Chapter 3. Protein structure and function. Proteins are the most versatile macromolecules in living...
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Transcript of Chapter 3. Protein structure and function. Proteins are the most versatile macromolecules in living...
Chapter 3. Protein structure and function
Proteins
are the most versatile macromolecules in living systems.
serve crucial functions in essentially all biological processes.
functions as catalysts.
Several key properties of proteins
1.Proteins are linear polymers built of monomer units called amino acids.
2.Proteins contained a wide range of functional groups. (alcohols, thiols, thioesters, carboxylic acids, basic groups)
3. Proteins can interact with one another and with other biological macormolecues to form complex assembles.
4. Some proteins are quite rigid, whereas others display limited flexibility.
- Only L amino acids are found in proteins.
Proteins are built from a repertoire of 20 amino acids
The L and D isomers of amino acids.
Ionization state as a function of pH
Peptide bonds are quite stable kinetically because the rate of hydrolysis is extremely slow
Primary structure: amino acids are linked by Peptide bonds to from polypeptides chains
Amino acid sequences have direction
Main chain or backbone: H bond donor-NH, H bond acceptor-CO,
Side chain: dependent on residues
The mean molecular weight of amino acid residue is ~110 g/mol (Da)
Components of polypeptide chain
Disulfide bond: Cross-links
Disulfide bond: Cross-links
Amino acid sequence of bovine insulin
Intra-molecule disulfide bond Inter-molecule disulfide bond
Proteins have unique amino acid sequences
knowing a.a. sequences is important for several reasons.
Knowledge of AA sequence 1. is essential to elucidating its mechanism of action.2. determine the 3D structures of proteins3. is a component of molecular pathology4. reveal much about its evolutionary history
Peptide bond is planar
Polypeptide chains are flexible yet conformationally restricted.
Peptide bond has considerable double-bond character, which prevents rotation about this bond
Almost all peptide bonds in proteins are trans
Steric clashes between groups attached to the alpha-carbon hinder formation of the cis form
Trans and cis X-pro bonds.The energies of these froms are realtively balaced because stric clashes occur in both forms
Most common cis peptides are X-proline linakges
In contrast with peptide bonds, the bonds btwn the amino group and the a-carbon atom and btwn the a-carbon and C-group are single bond.
This freedom of rotation about two bonds of each amino acid allows proteins to fold in many different ways.
By convention, both φand ψare defined as 0 when the twopeptide bonds flanking that carbon are in the same plane and positioned as shown.
The conformations of peptides are defined by the values of φand ψ. Conformations deemed possible are those that involve little or no steric interference, based on calculations using known van der Waals radii and bond angles.
Secondary Structure: Spatial arrangement of amino acid residues
Polypeptide chains can fold into regular structures such as the alpha helixbeta sheet, and turns and loops.
Alpha Helix
Structure of -helix
The CO group of each amino acid forms a hydrogen bond with the NH group of the amino acid that is situated four residues ahead in the sequence.
Q) Why does the α helix form more readily than many other possible conformations?
A) in part, an α helix makes optimal use of internal hydrogen bonds.
H-bond scheme for an -helix
Right handed Helices: 손가락 기준으로 시계반대방향Left handed Helices: 손가락 기준으로 시계방향
Five different kinds of constraints affect the stability of an α helix
(1)the electrostatic repulsion (or attraction) between successive amino acid residues with charged R groups
(2) the bulkiness of adjacent R groups
(3) the interactions between R groups spaced three (or four) residues apart
(4) the occurrence of Pro and Gly residues
(5) the interaction between amino acid residues at the ends of the helical segment and the electric dipole inherent to the α helix.
β-sheets
A β-strand is almost fully extended rather than being tightly coiled as in the α helix.
Structure of a β-strand
Anti-parallel arrangement
Parallel arrangement
Simple H-bonds
Complicated H-bonds
Polypeptide chains can change direction by making reverse turns or loops
Reverse turn = -turn = hairpin bend
Loops = omega Loops
Beta-Turn: connect the ends of two adjacent segmentsof an antiparallel β sheet
Structure of a reverse turnH-bond: CO of i and NH of i+3
Loops: no structural characteristics, more elaborate structurea responsible for chain reversal
Loops on a protein surface
Surface loops that mediate interactions with other molecules
Antibody
Tertiary structure: Protein ArchitectureThe overall three-dimensional arrangement of all atoms in a protein
Fibrous proteins, having polypeptide chains arranged in long strands or sheetsex: alpha-keratin
Globular proteins, having polypeptide chains folded into a spherical or globular shapeex: myoglobin
Myoglobin: the first protein to be seen in atomic level
Three dimensional structure of myoglobin
Quaternary structure:
Spatial arrangement of subunits and the nature of their interactions
The teramer structure of human hemoglobin
The amino acid sequence of a protein determines its three dimensional structure
1. Amino acids have different properties for forming -helix, sheets and turns
2. Protein folding is highly cooperative process.
3. Proteins fold by progressive stabilization of intermediates rather than random search
4. Prediction of three D structure from sequence remains a great challenge.
5. Protein modification and cleavage confer new capabilities