Packing is a key selection factor in the evolution of protein hydrophobic cores.


Abstract

The energy derived from optimized van der Waals interactions in closely packed, folded proteins has been proposed to be of similar energetic magnitude to hydrophobicity in stabilizing the native state. If packing is this energetically important, it should influence the evolution of protein core sequences. To test this hypothesis, the occurrence of various amino acid side chains in the major hydrophobic core of staphylococcal nuclease and 42 homologous proteins was determined. Most such positions in this protein family are usually isoleucine, leucine, or valine. Previously we have constructed and measured the stabilities of 12 single, 44 double, 64 triple, and 32 quadruple mutants, representing all possible permutations of these three side chains at two overlapping sets of four positions in the core of staphylococcal nuclease. The stabilities and interaction energies of those mutants with various combinations of the most common, or consensus, sequence were compared to the stabilities of all other mutants. Mutants which had the consensus side-chain combinations were not necessarily the most stable, but usually were found to have the best interaction energies. In other words, these proteins were far more stable than would be predicted from simply summing the observed energetic effects of the component single mutations, apparently reflecting particularly favorable packing interactions that are possible for the most common side chains. An additional 12 mutants which tested possible alternate explanations of the results were constructed. The stabilities and interaction energies of these mutants also support the conclusion that packing is a crucial determinant guiding the sequence evolution of protein cores. Study holds ProTherm entries: 12578, 12579, 12580, 12581, 12582, 12583, 12584 Extra Details: van der Waals interactions; hydrophobicity; hydrophobic core,interaction energies; packing

Submission Details

ID: BkByhYp74

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:43 p.m.

Version: 1

Publication Details
Chen J;Stites WE,Biochemistry (2001) Packing is a key selection factor in the evolution of protein hydrophobic cores. PMID:11735410
Additional Information

Sequence Assay Result Units