Opposing structural changes in two symmetrical polypeptides bring about opposing changes to the thermal stability of a complex integral membrane protein

Arch Biochem Biophys. 2011 Jan 15;505(2):160-70. doi: 10.1016/j.abb.2010.09.029. Epub 2010 Oct 8.

Abstract

The relationship between membrane protein structure and thermal stability has been examined in the reaction centre from the bacterium Rhodobacter sphaeroides, a complex membrane protein comprising three polypeptide chains and 10 cofactors. The core of this protein exhibits an approximate twofold symmetry, the cofactors being held in two membrane-spanning branches by two polypeptides, termed L and M, that have very similar folds. In assays of the thermal stability of wild-type and mutant reaction centres embedded in the native bilayer membrane, replacement of a Phe at position 197 of the M polypeptide by His produced an increase in stability, whereas an opposing replacement of His by Phe at the symmetrical position 168 of the L-polypeptide produced a decrease in stability. In light of the known X-ray crystal structures of wild-type and mutant variants of this protein, and further mutagenesis, it is concluded that these stability changes result from the introduction or removal, respectively, of a hydrogen bond between the side-chain of the His and that of an Asn located two positions along the M or L polypeptide chain, in addition to a hydrogen bond between the His side-chain and an adjacent bacteriochlorophyll cofactor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Coenzymes / chemistry
  • Coenzymes / metabolism
  • Enzyme Stability
  • Hydrogen Bonding
  • Kinetics
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Mutation
  • Peptides / chemistry*
  • Photosynthetic Reaction Center Complex Proteins / chemistry*
  • Photosynthetic Reaction Center Complex Proteins / genetics
  • Photosynthetic Reaction Center Complex Proteins / metabolism*
  • Protein Conformation
  • Protein Engineering
  • Protein Unfolding
  • Rhodobacter sphaeroides
  • Temperature*

Substances

  • Coenzymes
  • Membrane Proteins
  • Peptides
  • Photosynthetic Reaction Center Complex Proteins