Amino Acids, peptides, proteins II Flashcards
Levels of structure?
four levels of protein structures: primary, secondary, tertiary, and quaternary.
The primary structure of a protein refers to the amino acid sequence of a protein when amino acids are joined together to form the linear protein chain (also referred to as the polypeptide chain).
The protein chain folds itself to form local secondary structures.
The secondary structures interact with each other to form three-dimensional tertiary structures.
Sometimes more than one protein chain comes together to form quaternary structures.
Key elements of primary structure
AAs are joined together by the peptide bond formed between the carboxyl group of the 1st AA and the amino group of the 2nd AA.
Multiple AAs join to form a linear polypeptide chain (we often refer to each AA in the chain as a residue).
There are 3 kinds of covalent bonds in a polypeptide backbone:
1.) the bond between C-alpha and the carbonyl carbon within the first AA;
2.) the peptide bond between the carbonyl carbon of the first amino acid and the amide nitrogen of the second amino acid (where protease cuts!!!)
3.) the bond between the amide nitrogen and Ca of the second amino acid.
The peptide bond has partial double bond property and cannot be rotated, but the other two covalent bonds can be rotated. These rotations are expressed as dihedral angles phi (the angle around the Ca and amide nitrogen bond) and psi (the angle around the Ca and the carbonyl carbon bond). Not all phi and psi angles are possible because some rotations cause steric crowding of the backbone atoms. The possible phi and psi angles are clustered in small regions of a Ramachandran plot.
What determines fx of protein?
Its AA sequence. Similar sequence, similar fx.
Many proteins are polymorphic, meaning that these proteins have slightly different AA sequences at non-essential positions in each individual.
Proteases
There are general proteases that digest any peptide bond, such as trypsin, chymotrypsin, and pepsin, which are important proteases that BREAK DOWN protein in food in the digestive system.
There are other proteases that digest specific peptide bonds. These specific proteases often serve to ACTIVATE a particular enzyme through peptide bond cleavage. For example, many blood clotting factors are proteases normally existing in their inactive form. Upon trauma or surface damage, the most upstream clotting factor is cleaved and converted into active protease that triggers further cleavage of DOWNSTREAM clotting factors.
Hydrogen bond
Between protein backbone and amide nitrogen and carbonyl oxygen are driving force for formation of protein 2’ structures
H binds N, O, or F
Common donor is NH of backbone, common acceptor is O of peptide backbone (this is DRIVING force for formation of protein secondary structures). Acceptors tend to have OH groups.
Higher order structures
The 2 major types of secondary structures are the alpha helix and the beta pleated sheet (or simply called the beta sheet).
The turns and loops connect alpha helix or beta sheet to form tertiary structures.
Left handed triple helix is a unique secondary structure present in collagens and is important for the function of collagen.
Alpha-helices and H bonds
In an alpha helix, hydrogen bonds are formed between the carbonyl oxygen of the nth amino acid and the amide nitrogen of the n+4th amino acid within the SAME polypeptide chain. These hydrogen bonds force the polypeptide chain to form a right-handed screw-like helical structure.
Side chains in alpha-helices
All side chains of amino acids in an alpha helix point outward from the helix. The first and eighth residues in a helix are aligned nicely on top of each other. Some amino acids (for example Ala and Leu) have a higher tendency to form alpha helices but other amino acids (Pro and Gly) cannot form secondary structures such as alpha helices.
Example of a protein in alpha-helices
30% of all secondary structures.
An example of proteins that is mainly alpha helical is hemoglobin. Thalassemia is a genetic disease where mutations often cause the instability of alpha helices in hemoglobin.
Beta-sheet H bonds
In a beta sheet, hydrogen bonds are formed between two polypeptide chains. The two chains can be arranged in parallel or anti-parallel fashions.
Beta-sheet example
An example of protein which is mainly composed of beta sheets is immunoglobulin or antibody.
How do you measure the secondary structure content of a protein?
Circular Dichroism, which uses light.
Tertiary structure
Turns and loops connect alpha helix or beta sheets to form tertiary structures.
