• Unit I: What Makes a Cell (Chapters 1-3

)
– Introduction to Cells / The study of cells

– Molecules of Life and Bioenergetics
• Physiology in Focus: Metabolic Disorders

– Proteins – see Revised Chapter 3 Key Terms/Concept Sheet on ELMS!!!
Exam 1: Monday 2/13/17

Format: Multiple Choice, Short Answer, Matching
Study Materials:
• Lecture Slides
• Chapter Key Terms/Concept Sheets
• Practice Problems (similar types of questions will be on exam)

What do proteins do? a) binding . How is protein structure related to protein function? III. What are the factors that determine the structure and shape of proteins? II. Chapter 3 Questions/Objectives I.

high temperature. but it will refold spontaneously once the disruptor is removed urea disrupts noncovalent interactions within proteins Other denaturation agents: pH.I Disruption of a protein’s environment can unfold (denature) the protein. salt concentration Figure 3-6a Molecular Biology of the Cell (© Garland Science 2008) 3 .

II Tertiary structures can form ‘DOMAINS’ within a protein Protein domain: 3D Structural unit of a protein with uniquely defined binding/functional properties that often act independently of the rest of the protein Three tertiary structures within this protein form 3 separate Domains .

Different domains of a protein often II have different functions Catalytic domain Inhibits host cell protein synthesis Receptor binding domain (attaches to cell surface) Hydrophobic domain (Inserts into membranes) Diptheria Toxin 3 functional domains .

can also be described according their structure • Alpha helical domains • Coiled-coiled domains • Beta-sheet domains • Random coil domains (no secondary structure) .II Protein Domains .

Interactions between secondary structures II can form functional protein DOMAINS Alpha helices can wrap around one another to form coiled-coils “Coiled coil” alpha helices held together by “stripe” of hydophobic amino acid R groups (red) Single alpha helix Figure 3-9 Molecular Biology of the Cell (© Garland Science 2008) 7 .

g. yet share the same DNA-binding motif composed of three alpha helices 8 . a DNA-binding motif Common ribbon structure Red = Drosophila protein’s backbone Green = yeast protein’s backbone These two DNA-binding proteins are separated by a billion years of evolution.II Similar domains which occur in many related proteins are called sometimes called motifs – e.

Today’s Questions/Objectives I. What are the factors that determine the structure and shape of proteins? II. What do proteins do? a) binding b) distinct functional classes . How is protein structure related to protein function? III.

.IIIa Proteins Interact with other Molecules A protein’s physical interaction with other molecules determines its biological properties. small organic molecles • Other biomolecules (lipids. it is reversible. All proteins bind to other molecules • Ions. nucleic acids. ligands carbohydrates) • other proteins Because ligand binding is achieved by noncovalent bonds.

.IIIa Protein-ligand Interactions Can be weak and short-lived Can be tight and stable Are ALWAYS specific A given protein is usually only capable of interacting with only a few other molecules out of the thousands of different types in its environment.

Hence the importance of correct folding for protein function Figure 3-37a Molecular Biology of the Cell (© Garland Science 2008) . IIIa Ligand Binding sites are 3 dimensional The amino acids that contribute to binding a ligand are often quite far apart on a protein’s primary sequence but come together when the protein folds.

IIIa Close-up view of a binding site ligand Figure 3-37b Molecular Biology of the Cell (© Garland Science 2008) .

IIIa A protein’s structure and binding properties can be altered by covalent modifications • Covalent modifications: covalent linkages between a protein and some other molecule. • Our focus: – Phosphate groups – Acetyl Groups – Ubiquitin .

IIIa Covalent modifications to proteins: Phosphorylation Transfer of phosphate groups to a protein 3 Target amino acids: Ser. Thr. Tyr The presence of a phosphate group Phosphate groups are only added to these 3 on a protein enables new amino acids: electrostatic attractions/repulsions. This can cause changes in a protein’s: • Conformation/Shape • Localization in the cell • Binding properties Change in protein function .

IIIa Covalent modifications to proteins: Acetylation Transfer of acetyl groups Target amino acid: Lysine (LYS) Acetylases Deacetylases Removes the electrostatic property of the Lys R group .

IIIa Covalent modifications to proteins: Ubiquitylation Transfer of the ubiquitin protein Ubiquitin Target amino acid: Lysine (LYS) Small cytosolic protein (76 amino acids) Covalently attached to proteins (reversible) Serves as a tag that can either: mark proteins for degradation. or direct proteins to specific locations in the cell Isopeptide bond: formed between the COOH terminus of ubiquitin and the lysine R group of the protein target .

IIIa Ubiquitylation of Proteins occurs at lysine amino acids protein protein Lysine Lysine Ub Ub Lysine Ub monoubiquitylation polyubiquitylation Lysine Ub Directs Protein degradation Directs Protein localization in the cell .

Figure 3-81c Molecular Biology of the Cell (© Garland Science 2008) . IIIa Many proteins are covalently modified in multiple ways at multiple sites A protein’s function/behavior can be regulated by different combinations of modifications.