Driving forces for transmembrane alpha-helix oligomerization.
We present what we believe to be a novel statistical contact potential based on solved structures of transmembrane (TM) alpha-helical bundles, and we use this contact potential to investigate the amino acid likelihood of stabilizing helix-helix interfaces. To increase statistical significance, we have reduced the full contact energy matrix to a four-flavor alphabet of amino acids, automatically determined by our methodology, in which we find that polarity is a more dominant factor of group identity than is size, with charged or polar groups most often occupying the same face, whereas polar/apolar residue pairs tend to occupy opposite faces. We found that the most polar residues strongly influence interhelical contact formation, although they occur rarely in TM helical bundles. Two-body contact energies in the reduced letter code are capable of determining native structure from a large decoy set for a majority of test TM proteins, at the same time illustrating that certain higher-order sequence correlations are necessary for more accurate structure predictions.
Sodt
Alex J
AJ
Department of Bioengineering, University of California, Berkeley, California, USA. alexsodt@berkeley.edu
Head-Gordon
Teresa
T
D020816:Amino Acid Motifs; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D008954:Models, Biological; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D013816:Thermodynamics
D008565:Membrane Proteins