Four levels of protein structure exist:
- Primary structure: the genetically determined sequence of amino acid residues
- Secondary structure: regular, local conformations, chiefly a-helices and b-sheets, stabilized by hydrogen bonding between backbone NH and C=O groups
- Tertiary structure: folding of the protein chain into a compact shape stabilized largely by lipophilic interactions between amino acid side chains
- Electrostatic interactions ("salt bridges") between charged side chains also play a role
- The interior of the structure is largely close-packed
- Quaternary structure: assembly of multiple protein chains into a functional protein, again stabilized largely by lipophilic interactions
Although classification systems vary, proteins appear to be constructed of a limited number of domain types, built from a limited number of simple motifs. That is, evolution has not made use of the full range of conformation space available to proteins.
S.-H. Kim's group at Berkeley et al. [Proc. Nat. Acad. Sci., 2003, 100, 2386; 2005, 102, 618; 2005, 102, 3651; Protein Sci., 2006, 15, 1723] attempted to define the conformation space used.
- They calculated measures of pairwise structural similarity among the 1898 proteins in the PDB Select Database
- The calculations used 25,000 cpu hours on an IBM RS 6000
- The results were mapped onto a three-dimensional paramaeter space, roughly described as a, b, and a/b:
|The Use of Protein Conformation Space
Here's the same idea, mapped onto Ramachandran diagrams:
|Ramachandran Diagrams of Conformation Space
- For these diagrams, the proteins were broken into 6-9 residue segments
- The second diagram transforms the first from 0-180 degrees to 0-360 degrees.
Soding and Lupas [BioEssays, 2003, 25, 837] note that structural homology is substantially more conserved through evolution than is sequence homology. They argue that:
- Modern proteins evolved by fusion of simpler "building block" proteins
- Each of these simpler proteins represents a conserved fold
- Here are some of their suggestions:
Some issues that are not completely resolved:
- To what extent do crystal structures reflect structures in solution ?
- Substantial evidence now exists that many proteins are conformationally heterogeneous in solution
- However, many small organic molecules that are conformationally heterogeneous in solution crystallize in a single conformation
- To what extent do structures in solution or in crystals reflect structures within the cell ?
- Many proteins exist within cells in complexes with other proteins or bound to structural elements of the cell
This page last modified 1:59 PM on Thursday February 10th, 2011.
Webmaster, Department of Chemistry, University of Maine, Orono, ME 04469