Building blocks of proteins are called Amino Acids.

All proteins contain the elements Carbon, Hydrogen, Oxygen and Nitrogen.
 Amino Acids contain the -NH2 group which is called the amino

group  And the COOH group or the Carboxyl group.  Amino Acids are defined by the side group or R-Group.

 The bond that holds amino acids together is called a peptide bond.
 When two more amino acids are put together they become a polypeptide.

 The order in which amino acids are placed in the chain

determines the structure of the protein.

 The structure of the protein determines

the function of the protein.

From amino acids to protein:

N-terminus terminates by an amino group

Peptide bond

Amino acid

C-terminus terminates by a carboxyl group
A peptide: Phe-Ser-Glu-Lys (F-S-E-K)

The Shape of proteins:

Occurs Spontaneously Native conformation

determined by different Levels of structure

Non covalent interactions involved in the shape of proteins

Four Levels of Structure Determine the Shape of Proteins
Primary structure
The linear arrangement (sequence) of amino acids and the location of covalent (mostly disulfide) bonds within a polypeptide chain. Determined by the genetic code.

Secondary structure

local folding of a polypeptide chain into regular structures including the a helix, b sheet, and U-shaped turns and loops.

Tertiary structure
overall three-dimensional form of a polypeptide chain, which is stabilized by multiple non-covalent interactions between side chains.

Quaternary structure:
The number and relative positions of the polypeptide chains in multisubunit proteins. Not all protein have a quaternary structure.

Primary Structure
C-peptide

Pro-insulin protein

Pro-insulin is produced in the Pancreatic islet cells
30/31

65/66 Human: Thr-Ser-Ile Cow: Ala-Ser-Val Pig: Thr-Ser-Ile Chiken: His-Asn-Thr

Insuline C-peptide + C peptide

Protein conformation: most of the proteins fold into only one stable conformation or native conformation

More than 50 amino acids becomes a protein

Protein conformation: most of the proteins fold into only one stable conformation or native conformation

More than 50 amino acids becomes a protein

SECONDARY STRUCTURE
 Stabilized by hydrogen bonds

 H- bonds are between –CO and –NH groups of

peptide backbone  H-bonds are either intra- or inter- molecular  3 types : a-helix, b-sheet and triple-helix
a Helix: a helix conformation was discovered 50 years ago in a keratine abundant in hair nails, and horns b Sheet: discovered within a year of the discovery of a helix. Found in protein fibroin the major constituant of silk

The a helix:
result from hydrogen bonding, does not involve the side chain of the amino acid

bsheet:
result from hydrogen bonding, does not involve the side chain of the amino acid

Two type of b Sheet structures
An anti paralellel b sheet

A paralellel b sheet

TRIPLE HELIX
 Limited to tropocollagen molecule  Sequence motif of –(Gly-X-Pro/Hypro)n 3 left-handed helices wound together to give a

right-handed superhelix  Stable superhelix : glycines located on the central axis (small R group) of triple helix  One interchain H-bond for each triplet of aas – between NH of Gly and CO of X (or Proline) in the adjacent chain

Triple helix of Collagen

NONREPETITIVE STRUCTURES
 Helices/b-sheets: ~50% of regular

2ostructures of globular proteins  Remaining : coil or loop conformation  Also quite regular, but difficult to describe  Examples : reverse turns, b-bends (connect successive strands of antiparallel b-sheets)

The Beta Turn
(aka beta bend, tight turn)  allows the peptide chain to reverse direction  carbonyl O of one residue is H-bonded to the amide proton of a residue three residues away  proline and glycine are prevalent in beta turns (?)

b-bulge
 A strand of polypeptide in a b-sheet may contain an “extra” residue  This extra residue is not hydrogen bonded to a neighbouring strand  This is known as a b-bulge.

Tertiary structure: the overall shape of a protein

The secondary structure of a telephone cord A telephone cord, specifically the coil of a telephone cord, can be used as an analogy to the alpha helix secondary structure of a protein.

The tertiary structure of a telephone cord The tertiary structure of a protein refers to the way the secondary structure folds back upon itself or twists around to form a threedimensional structure. The secondary coil structure is still there, but the tertiary tangle has been superimposed on it.

Tertiary structure: the overall shape of a protein
Full three dimensional organization of a protein

 R-group interactions result in 3D

structures of globular proteins  Types of interactions : H-, ionic(salt linkage), hydrophobic- and disulphide- bond  Hydrophilic R groups on surface while hydrophobic R groups buried inside of molecule  Wide variety of 3o structures: since large variation in protein sizes and amino acid sequences

The three-dimensional structure of a protein kinase

The role of side chain in the shape of proteins
Hydrophili c

Hydrophobic

A coiled-coil:
Structure occurs when the 2 a helix have most of their nonpolar (hydrophobic) side chains on one side, so that they can twist around each other with these side chain facing inwards

Quaternery structure:
If protein is formed as a complex of more than one protein chain, the complete structure is designed as quaternery structure: • Generally formed by noncovalent interactions between subunits • Either as homo- or hetero-multimers

QUATERNARY STRUCTURE: ADVANTAGES
 Oligomers (multimers) are more stable than dissociated subunits
 They prolong life of protein in vivo

 Active sites can be formed by residues from adjacent subunits/chains
 A subunit may not constitute a complete active site

 Error of synthesis is greater for longer polypeptide chains
 Subunit interactions : cooperativity/ allosteric effects

Primary structure

Secondary structure

Tertiary structure

Quaternary structure

Protein domains:
Any part of a protein that can fold independently into a compact, stable structure. A domain usually contains between 40 and 350 amino acids.

• A domain is the modular unit from which many larger proteins are constructed. • The different domain of protein are often associated with different functions.

Protein domains
Cytochrome b562 A single domain protein involved in electron transport in mitochondria The NAD-binding domain of the enzyme lactic dehydrogenase The variable domain of an immunoglobulin

Protein Folding
is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil.[1] Each protein exists as an unfolded polypeptide or random coil when translated from a sequence ofmRNA to a linear chain of amino acids. This polypeptide lacks any developed three-dimensional structure. Amino acids interact with each other to produce a well-defined three dimensional structure, the folded protein, known as the native state. The resulting threedimensional structure is determined by the amino acid sequence.

For many proteins the correct three dimensional structure is essential to function. Failure to fold into the intended shape usually produces inactive proteins with different properties including toxic prions. Several neurodegenerative and other diseases are believed to result from the accumulation of misfolded (incorrectly folded) proteins. Many allergies are caused by the folding of the proteins, for the immune system does not produce antibodies for certain protein structures.

Function of proteins
• Enzymatic catalysis • Transport and storage (the protein hemoglobin, albumins) • Coordinated motion (actin and myosin). • Mechanical support (collagen). • Immune protection (antibodies) • Generation and transmission of nerve impulses - some amino acids act as neurotransmitters, receptors for neurotransmitters, drugs, etc. are protein in nature. (the acetylcholine receptor), • Control of growth and differentiation - transcription factors Hormones growth factors ( insulin or thyroid stimulating hormone)

Enzymes
 Enzymes are proteins that catalyze (i.e. speed up)

chemical reactions. Enzymes are catalysts.  Enzymes work on things called Substrates  Each enzyme is specific for its substrate  Almost all processes in a cell need enzymes in order to occur at significant rates.
 Enzymes are not used up by the reaction.  After they have done their work they release the products

and are not changed  Each enzyme can work on many molecules of the substrate

Lock and Key Model
 The method in which enzymes work is called the lock

and key model

Transport and storage - small molecules are often carried by proteins
in the physiological setting (for example, the protein hemoglobin is responsible for the transport of oxygen to tissues). Many drug molecules are partially bound to serum albumins in the plasma.
The binding of oxygen is affected by molecules such as carbon monoxide (CO) (for example from tobacco smoking, cars and furnaces). CO competes with oxygen at the heme binding site. Hemoglobin binding affinity for CO is 200 times greater than its affinity for oxygen, meaning that small amounts of CO dramatically reduces hemoglobin's ability to transport oxygen. When hemoglobin combines with CO, it forms a very bright red compound called carboxyhemoglobin. When inspired air contains CO levels as low as 0.02%, headache and nausea occur; if the CO concentration is increased to 0.1%, unconsciousness will follow. In heavy smokers, up to 20% of the oxygen-active sites can be blocked by CO.

3-dimensional structure of hemoglobin. The four subunits are shown in red and yellow, and the heme groups in green.

Coordinated motion - muscle is mostly protein, and muscle contraction is
mediated by the sliding motion of two protein filaments, actin and myosin.

Platelet activation is a controlled sequence of actin filament: Severing Uncapping Elongating Cross linking That creates a dramatic shape change in the platelet

Platelet before activation

Activated platelet

Activated platelet at a later stage than C)

Mechanical support –
skin and bone are strengthened by the protein collagen.

Abnormal collagen synthesis or structure causes dysfunction of
• cardiovascular organs, • bone, • skin, • joints • eyes
Refer to Devlin Clinical correlation 3.4 p121

Immune protection - antibodies are protein structures that are
responsible for reacting with specific foreign substances in the body.

Generation and transmission of nerve impulses
Some amino acids act as neurotransmitters, which transmit electrical signals from one nerve cell to another. In addition, receptors for neurotransmitters, drugs, etc. are protein in nature. An example of this is the acetylcholine receptor, which is a protein structure that is embedded in postsynaptic neurons.
GABA: gamma Amino butyric acid Synthesised from glutamate
GABA acts at inhibitory synapses in the brain. GABA acts by binding to specific receptors in the plasma membrane of both pre- and postsynaptic neurons. Neurotransmetter

Control of growth and differentiation proteins can be critical to the control of growth, cell differentiation and expression of DNA.

For example, repressor proteins may bind to specific segments of DNA, preventing expression and thus the formation of the product of that DNA segment. Also, many hormones and growth factors that regulate cell function, such as insulin or thyroid stimulating hormone are proteins.

 DNA is found packed in the nucleus of

eukaryotic organisms; it is found in the cytoplasm of prokaryotic organisms  DNA is packed together and wrapped around special proteins called HISTONES  DNA bound protein is called CHROMATIN  When chromatin condenses (gets thicker) it forms CHROMOSOMES

Nucleosome
Chromosome DNA double helix

Coils

Supercoils

Histones

DNA Structure
 Double Helix - twisted ladder  Made up of monomers

called nucleotides
 Nucleotides are composed of:  Deoxyribose sugar  Phosphate group  Nitrogenous base

Nitrogenous Bases
 Two types:  Purines (two rings)  Pyrimidines (one ring)
 Purines  Adenine and Guanine  Pyrimidines  Thymine and Cytosine

Purines

Pyrimidines
Cytosine Thymine

Adenine

Guanine

Phosphate group

Deoxyribose

Bonding
TEMPLATE STRAND

A

C

G

G

T

A

T

G

C

C

A

T

Weak HYDROGEN bonds form between the Nitrogen Base Pairs.

Chargaff’s rules:
 Base pairing rule is A-T and G-C
 Thymine is replaced by Uracil in RNA  Bases are bonded to each other by Hydrogen bonds

 Discovered because of the relative percent of each

base; (notice that A-T is similar and C-G are similar)

DNA Structure
Backbone alternates with phosphate & sugr/deoxyriboes with the nucleotides forming the rungs or steps of the ladder

The backbone of it all…
TEMPLATE STRAND

A

C

G

G

T

A

T

G

C

C

A

T

The backbone is made of alternating sugars and phosphates. - Remember: Sugar ALWAYS attaches to the Nitrogen base

Decoding the Information in DNA
 How does DNA (a twisted latter of atoms) control

everything in a cell and ultimately an organism?  DNA controls the manufacture of all cellular proteins including enzymes  A gene is a region of DNA that contains the instructions for the manufacture of on particular polypeptide chain (chain of amino acids) DNA is a set of blueprints or code from making proteins

Genetic Code
 Genetic code – the language of mRNA

instructions (blueprints)  Read in three letters at a time  Each letter represents one of the nitrogenous bases: A, U, C, G
 Codon found on mRNA; consists of three bases

(one right after the other)  64 codons for 20 amino acids

Codon (cont’d)
 For example, consider the following RNA

sequence: UCGCACGGU The sequence would be read three base pairs at a time: UCG – CAC – GGU The codons represent the amino acids:  Serine – Histidine – Glycine  AUG – start codon or Methionine  UAA, UAG, UGA – stop codons; code for nothing; like the period at the end of a sentence

The gene-enzyme relationship has been revised to the one-gene, one-polypeptide relationship. Example: In hemoglobin, each polypeptide chain is specified by a separate gene. Other genes code for RNA that is not translated to polypeptides; some genes are involved in controlling other genes.

DNA & RNA
 Before mitosis (during S phase of interphase) , a complete copy of a cell’s DNA is made through a process called replication.  When a cell divides, each daughter cell gets one complete copy of the DNA.  Similar to photocopying a document – the end

result is two identical documents that contain the same information.  Now that we know something about DNA’s structure, lets look at how it replicates.

Steps of DNA Replication
DNA must unwind and break the hydrogen bonds 2) Each strand is used as a template (blueprint) 3) Two new strands of DNA are formed from the original strand by the enzyme DNA Polymerase
1)

DNA Transcription

 During replication, an enzyme called helicase “unzips” the

DNA molecule along the base pairing, straight down the middle.  Another enzyme, called DNA polymerase, moves along the bases on each of the unzipped halves and connects complementary nucleotides.

From Gene to Protein

Synthesis of DNA from RNA is reverse transcription. Viruses that do this are Retroviruses.

Differences between DNA and RNA
DNA  Structure:
 Double stranded

RNA  Structure:
 Single-stranded

 Sugar: Deoxyribose

Bases:  Adenine  Guanine  Cytosine  Thymine

 Sugar: Ribose

Bases:  Adenine  Guanine  Cytosine  Uracil

ow do you get from DNA to Proteins?

TRANSCRIPTION – the synthesis of RNA under the direction of DNA TRANSLATION – the actual synthesis of a protein, which occurs under the direction of mRNA

Splicing
Each gene has it own promotor Each gene is widely spacied The information is fragmented Exon = expressed gen Intron = intervening part
Alternative splicing: A regulatory mechanism by which variations in the incorporation of a gene’s exons, or coding regions, into messenger RNA lead to the production of more than one related protein, or isoform. Alternative splicing is a source of genetic diversity in eukaryotes. Splicing has been used to account for the relatively small number of genes in the human genome.

mRNA Splicing

The entire gene is transcripted into a message. Some of the message is Junk (introns) and is removed before exiting the nucleus. A spliceosome is a complex of specialized RNA and protein that removes introns from a pre-mRNA This process is generally referred to as splicing. Introns typically have a ―GU‖ nucleotide sequence at the 5' end splice site, and an AG at the 3' end splice site.

Guttmacher and Collins , NEJM, 347 (19): 1512, Figure 2

November 7, 2002

Translation- the Ultimate Goal!
•Going from mRNA to the final product

Transcription- how RNA is made
 Just as DNA polymerase makes new DNA, a similar enzyme called RNA polymerase makes new RNA.  RNA polymerase temporarily separates the strands of a

small section of the DNA molecule. This exposes some of the bases of the DNA molecule.  Along one strand, the RNA polymerase binds complementary RNA nucleotides to the exposed DNA bases.  An exposed thymine on the DNA strand hooks up with an RNA nucleotide with an adenine; an exposed cytosine on the DNA hooks up with an RNA nucleotide with a guanine base; an exposed adenine DNA base will hook up with URACIL!

 As the RNA polymerase moves along, it makes a strand of messenger RNA (mRNA).  It is called messenger RNA because it carries DNA’s message out of the nucleus and into the cytoplasm.  mRNA is SINGLE STRANDED!  When the RNA polymerase is done reading the gene in the DNA, it leaves.  The separated DNA strands reconnect, ready to be read again when necessary.  mRNA moves out of the nucleus and finds a ribosome  On the ribosome, amino acids are assembled to form proteins in the process called translation.

Translation: Protein Synthesis
1)mRNA is transcribed in the nucleus and leaves the nucleus to the cytoplasm 2) mRNA attaches to the ribosome 3) tRNA carries the anticodon which pairs up with the codon on the mRNA 4) tRNA brings the correct amino acid by reading the genetic code 5) The amino acids are joined together to form a polypeptide (protein) 6) When a stop codon is reached (UAA, UAG, UGA) protein synthesis stops

Translation
mRNA

GUA

UCU

GUU

ACC

GUA

•mRNA carries the same message as DNA but rewritten with different nitrogen bases. •This message codes for a specific sequence of amino acids

•Review..Amino acids are the building blocks of…
•PROTEINS

SO:
 Say the mRNA strand reads:
 mRNA (codon)

AUG–GAC–CAG-UGA  tRNA (anticodon) UAC-CUG-GUC-ACU
 tRNA would bring the amino acids:  Methionine-Aspartic acid-Glutamine-stop

Translation
mRNA

GUA

UCU GUU

ACC

GUA

•Codon: a sequence of 3 nitrogen bases on mRNA that code for 1 amino acid
•It’s a TRIPLET code •Example: This strand of mRNA has 5 codons, so it would code for 5 amino acids.

Translation
mRNA

GUA

UCU

GUU

ACC

GUA

•These codons are universal for every bacteria, plant and animal on earth •There are 64 codons which code for all 20 amino acids on earth.

The genetic code: specifies which amino acids will be used to build a protein Codon: a sequence of three bases. Each codon specifies a particular amino acid.

Start codon: AUG—initiation signal for translation Stop codons: stops translation and polypeptide is released

Codons match up with anticodons to create a protein

Figure 12.6 The Genetic Code

Translation
mRNA

GUA

UCU

GUU

ACC

GUA

Ribosome

•The mRNA molecule travels to the ribosomes where the mRNA codes are ―read‖ by the ribosomes •Ribosomes hold the mRNA so another type of RNA, transfer RNA (tRNA) can attach to the mRNA

Translation
mRNA

GUA UCU

GUU

ACC

GUA

Ribosome

CA U

AG A

Translation
mRNA

GUA

UCU

GUU ACC

GUA

CA U A G A CA A

Elements of translation
 Ribosomes
 rRNA  Large and small subunits

 Initiation  Chain Elongation  Peptide bonds

 Codons
 Initiator or start codon  Methionine (AUG)  Stop codons  tRNA

 Chain termination
 Polysome

RNA
Ribonucleic acid
Single-stranded helix

Sugar is ribose
Thymine is replaced by URACIL

Major RNAs
mRNA
messenger RNA carries the genetic information that will be expressed ultimately as proteins. (carries information from

DNA to ribosome)

tRNA
transfer RNA is the adapter molecule. It recognizes the codons of the mRNA on the one hand, and it can be covalently bonded to the appropriate amino acid, on the other. (Carries amino acids)

rRNA
ribosomal RNA is found in the ribosomes (Makes up

ribosomes)

RNA-Coding Genes
A. B. C. D. E. F. G. H. I. Ribosomal RNA (rRNA) genes Transfer RNA (tRNA) genes Small Nuclear RNA (snRNA) genes Small Nucleolar RNA (snoRNA) genes Regulatory RNA genes XIST RNA-Coding Genes MicroRNA (miRNA) genes Antisense RNA genes Riboswitch genes

RNA

can be

Messenger RNA

Ribosomal RNA

Transfer RNA

also called

which functions to

also called

which functions to

also called

mRNA

Carry instructions

rRNA

Combine with proteins

tRNA

Bring amino acids to ribosome

from

to

to make up

DNA

Ribosome

Ribosomes

Processing the RNA transcript into mRNA
1. Mono-cistronic 2. Maturation
a) b)

c)

RNA capping RNA polyadenylation RNA splicing

Cistron = Gene

Maturation of Eukatriotic mRNA
 Intron: not founded in cytoplasm Cap: 7-Methyl-Guanosine cap, protect mRNA

from degradation and serve as a ribosome binding site Poly-A tail: AAUAAA (200 A’s) to protect the message from degradation  Splicing: remove of introns Lariat structures: introns removed from hnRNA (heterogeneus nuclear RNA) are degraded in nucleus

Transfer RNA

The conformation (three-dimensional shape) of tRNA results from base pairing (H bonds) within the molecule. 3' end is the amino acid attachment site—binds covalently. Always CCA. Anticodon: site of base pairing with mRNA. Unique for each species of tRNA.

Hydrogen bonds form between the anticodon of tRNA and the codon of mRNA. Small subunit rRNA validates the match—if hydrogen bonds have not formed between all three base pairs, it must be an incorrect match, and the tRNA is rejected.

Example: DNA codon for arginine: 3'-GCC-5' Complementary mRNA: 3'-CGG-5'

Anticodon on the tRNA: 3'-GCC-5' This tRNA is charged with arginine.

TAC - ___ ____ ____ - TAC

Wobble: specificity for the base at the 3' end of the codon is not always observed. Example: codons for alanine—GCA, GCC, and GCU—are recognized by the same tRNA.

Protein formation
 Amino acids link

together to form a protein  The new protein could become cell part, an enzyme, a hormone etc.

Ribosomic RNA
Prokaryotic ribosomes have 3 rRNA molecules: 23S, 16S and 5S. 2 Subunits: 50S+30S Eukaryotic ribosomes have 4 rRNA molecules: 28S, 18S, 5.8S and 5S 2 Subunits: 60S+40S

50S

30S

60S

40S

Ribosome: the workbench—holds mRNA and tRNA in the correct positions to allow assembly of polypeptide chain. Ribosomes are not specific, they can make any type of protein.

Prokaryotes Small Subunit 30s 16s 21 proteins

Large subunit 50s 5s 23s 34 proteins

Eukaryotes: Small 40S 18S 33 proteins

Large 60S 5S 28S 5.8S 49 proteins

**The numbers are not additive – based on centrifugation rates

Subunits are held together by ionic and hydrophobic forces (not covalent bonds). When not active in translation, the subunits exist separately.

Figure 12.10 Ribosome Structure

Large subunit has three tRNA binding sites:

• A site binds with anticodon of charged tRNA.
• P site is where tRNA adds its amino acid to the growing chain. • E site is where tRNA sits before being released.

RNA polymerases catalyze synthesis of RNA. RNA polymerases are processive—a single enzyme-template binding results in polymerization of hundreds of RNA bases.

Figure 12.4 RNA Polymerase

What are the bonds called that form between ribose bases?

Transcription occurs in three phases: • Initiation • Elongation

• Termination

http://vcell.ndsu.edu/animations/transcription/movie.htm

Initiation requires a promoter—a special sequence of DNA.

RNA polymerase binds to the promoter.
Promoter tells RNA polymerase where to start, which direction to go in, and which strand of DNA to transcribe. Part of each promoter is the initiation site.

DNA Is Transcribed to Form RNA (A)

http://www.biostudio.com/demo_freeman_pro tein_synthesis.htm

STEP 1

Step 2

Start codon is AUG; first amino acid is always methionine, which may be removed after translation. The large subunit joins the complex, the charged tRNA is now in the P site of the large subunit.

Elongation: RNA polymerase unwinds DNA about 10 base pairs at a time; reads template in 3' to 5' direction. The RNA transcript is antiparallel to the DNA template strand. RNA polymerases do not proof read and correct mistakes.

Elongation: the second charged tRNA enters the A site. Large subunit catalyzes two reactions: 1. Breaks bond between tRNA in P site and its amino acid. 2. Peptide bond forms between that amino acid and the amino acid on tRNA in the A site.

Termination: specified by a specific DNA base sequence. Mechanisms of termination are complex and varied.

Eukaryotes—first product is a pre-mRNA that is longer than the final mRNA and must undergo processing.

Termination: translation ends when a stop codon enters the A site. Stop codon binds a protein release factor—allows hydrolysis of bond between polypeptide chain and tRNA on the P site. Polypeptide chain—C terminus is the last amino acid added.

Table 12.1

Several ribosomes can work together to translate the same mRNA, producing multiple copies of the polypeptide. A strand of mRNA with associated ribosomes is called a polyribosome or polysome.

Figure 12.14 A Polysome (Part 1)

Figure 12.14 A Polysome (Part 2)

Stabilizing the message
Posttranslational aspects of protein synthesis:

 How is a message (mRNA) stabilized

1. 5’ cap added to N side of new protein

to get enough protein…at the right time?

5’ cap can enhance translation – go faster

2. Polyadenylation is the synthesis of a poly(A) tail, a stretch of adenines at the end of the mRNA molecule. At the end of transcription the last 3’ bit of the newly made RNA is cleaved off by a set aof enzymes. The enzymes then synthesize the poly(A) tail at the RNA's 3' end. The poly(A) tail is important for the nuclear export, translation and stability of mRNA. The tail is shortened over time and when it is short enough, the mRNA is degraded. In a few cell types, mRNAs with short poly(A) tails are stored for later activation

Processing the protein (product)
3. TARGETING: Polypeptide may be moved from synthesis site to an organelle, or out of the cell.
Amino acid sequence also contains a signal sequence—an ―address label.‖

i.e. – proteins targeted to ER 5-10 hydrophobic amino acids on the N-terminus.

Destinations for Newly Translated Polypeptides in a Eukaryotic Cell

A Signal Sequence Moves a Polypeptide into the ER (Part 1)

Figure 12.16 A Signal Sequence Moves a Polypeptide into the ER (Part 2)

Folding chaperones (proteins) in RER fold proteins appropriately.

Mis-folding diseases:
Altzheimer’s

Creutzfeld–Jakob disease (CJD) (prion disease)
P53 – cancer from misfolded ―watchdog‖

What Happens to Polypeptides after Translation?

4. Glycosylation: addition of sugars to form glycoproteins Sugars may be added in the Golgi apparatus—the resulting glycoproteins end up in the plasma membrane, lysosomes, or vacuoles. Diseases: incorrect addition of sugars to specific amino acids – shows in infancyalmost always involves nervous system development.

 All proteins inserted into or associated with

the cell membrane have sugars attached to them. They aid in recognition of other molecules.  What would be some consequences of incorrect glycosylation at the cell membrane?

What Happens to Polypeptides after Translation?

Protein modifications: 5. Proteolysis: cutting the polypeptide chain by proteases. Degradation of protein message.

6. Phosphorylation: addition of phosphate groups by kinases. Charged phosphate groups change the conformation. Generally makes protein into enzymes!

Posttranslational Modifications of Proteins

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