Protein Folding

• Proteins fold into one or more specific spatial conformations

driven by a number of non-covalent interactions such as
hydrogen bonding, ionic interactions, Van der Waals forces,
and hydrophobic packing.
• A polypeptide folds into its characteristic 3D structure from a
random coil.
• After translation the linear chain begins to fold into its three-
dimensional structure.
• Several neurodegenerative and other diseases
are believed to result from the accumulation
of amyloid fibrils formed by misfolded
proteins.
• Many allergies are caused by incorrect folding
of some proteins, because the immune system
does not produce antibodies for certain
protein structures.
Protein folding depends on;
• Solvent (water or lipid bilayer)
• Temperature
• pH
• Concentration of salt
• the possible presence of cofactors
• Molecular cheperons
Role of Cheperones
• Molecular chaperones are a class of proteins that aid in the
correct folding of other proteins.
• Chaperones exist in all cellular compartments and interact
with the polypeptide chain in order to allow the native 3D
conformation of the protein to form.
• Chaperones prevent aggregation and incorrect folding by
binding to and stabilizing partially or totally unfolded
polypeptides until the polypeptide chain is fully synthesized.
• Ensure the stability of unfolded chains.
• Each of the families of molecular chaperones
have their own functions e.g. the “heat shock
proteins” (Hsps), particularly the Hsp70 and
Hsp60 families.
Protein Structure
• Protein structure is the 3D arrangement of
atoms in an amino acid-chain.
• Under condensation reactions, amino acids lose
one water molecule per reaction in order to
attach to one another with a peptide bond.
• Protein structures range in size from tens to
several thousand amino acids.
• A protein usually undergoes reversible structural
changes in performing its biological function.
Process of protein folding
Following are some levels of Protein structure.
• Primary structure.
• Secondary structure.
• Tertiary structure.
• Quaternary structure.
Primary structure
• The primary structure is held together by peptide bonds that
are made during the process of protein biosynthesis.
• Reaction take place by peptide linkage between Amino group
(-NH2) of one amino acid to the Carboxyl group (-C=0) to the
next amino acid and water is produced.
• The primary structure of a protein is determined by the gene
corresponding to the protein.
• The sequence of amino acid residues can be read directly
from the sequence of the gene using the genetic code.
Secondary structure
• Formation of a secondary structure is the first step in the
folding process.
• The two most common secondary structural elements are;
alpha helices and beta sheets.
Alpha helices.
The amino acids in an α-helix are arranged in a right-handed
helical structure where each amino acid residue corresponds to
a 100° turn in the helix. In a right hand-helix conformation in
every backbone N−H group hydrogen bonds to the backbone
C=O group.
Beta sheets; secondary fold
• The β pleated sheet is a structure that forms with the
backbone bending over itself to form the hydrogen
bonds.
• The hydrogen bonds are between the amide hydrogen
and carbonyl oxygen.
• There exists anti-parallel β pleated sheets and parallel
β pleated sheets, hydrogen bonds are strongly stable
in the anti-parallel β sheet as it hydrogen bonds with
the ideal 180 degree angle compared to the slanted
hydrogen bonds formed by parallel sheets.
Tertiary structure
• The α-helixes and β-pleated-sheets are folded into a compact
globular structure.
• The folding is driven by hydrophobic interactions.
• It is generally stabilized by outside polar hydrophilic hydrogen
and ionic bond interactions, and internal
hydrophobic interactions.
• Tertiary folding begins while the protein
is being molded into its
primary polypeptide sequence.
• It is known to be guided
by chaperones.
Quaternary structure
• Quaternary structure is the arrangement of more than one
protein molecule in a multi-subunit complex.
• These subunits may be the same, as in a homodimer, or
different, as in a heterodimer.
• The final shape of the protein complex is once again stabilized
by various interactions, including hydrogen-bonding, disulfide-
bridges and salt bridges.
• Forexample hemoglobin.
• In hemoglobin, one protein
binds to oxygen while another
binds carbon dioxide.