Interstrand pairing patterns in β-barrel membrane proteins: The positive-outside rule, aromatic rescue, and strand registration prediction

Ronald Jackups, Jie Liang

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

β-Barrel membrane proteins are found in the outer membrane of Gram-negative bacteria, mitochondria, and chloroplasts. Little is known about how residues in membrane β-barrels interact preferentially with other residues on adjacent strands. We have developed probabilistic models to quantify propensities of residues for different spatial locations and for interstrand pairwise contact interactions involving strong H-bonds, side-chain interactions, and weak H-bonds. Using the reference state of exhaustive permutation of residues within the same β-strand, the propensity values and p-values measuring statistical significance are calculated exactly by analytical formulae we have developed. Our findings show that there are characteristic preferences of residues for different membrane locations. Contrary to the "positive-inside" rule for helical membrane proteins, β-barrel membrane proteins follow a significant albeit weaker "positive- outside" rule, in that the basic residues Arg and Lys are disproportionately favored in the extracellular cap region and disfavored in the periplasmic cap region. We find that different residue pairs prefer strong backbone H-bonded interstrand pairings (e.g. Gly-aromatic) or non-H-bonded pairings (e.g. aromatic-aromatic). In addition, we find that Tyr and Phe participate in aromatic rescue by shielding Gly from polar environments. We also show that these propensities can be used to predict the registration of strand pairs, an important task for the structure prediction of β-barrel membrane proteins. Our accuracy of 44% is considerably better than random (7%). It also significantly outperforms a comparable registration prediction for soluble β-sheets under similar conditions. Our results imply several experiments that can help to elucidate the mechanisms of in vitro and in vivo folding of β-barrel membrane proteins. The propensity scales developed in this study will also be useful for computational structure prediction and for folding simulations.

Original languageEnglish
Pages (from-to)979-993
Number of pages15
JournalJournal of Molecular Biology
Volume354
Issue number4
DOIs
StatePublished - Dec 9 2005
Externally publishedYes

Keywords

  • Aromatic rescue
  • Interstrand contact interactions
  • Positive-outside rule
  • Two-body potential
  • β-barrel membrane protein

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