The GxxxG motif: A framework for transmembrane helix-helix association

William P. Russ, Donald M. Engelman

Research output: Contribution to journalArticlepeer-review

729 Scopus citations


In order to identify strong transmembrane helix packing motifs, we have selected transmembrane domains exhibiting high-affinity homo-oligomerization from a randomized sequence library based on the right-handed dimerization motif of glycophorin A. Sequences were isolated using the TOXCAT system, which measures transmembrane helix-helix association in the Escherichia coli inner membrane. Strong selection was applied to a large range of sequences (~107 possibilities) and resulted in the identification of sequence patterns that mediate high-affinity helix-helix association. The most frequent motif isolated, GxxxG, occurs in over 80 % of the isolates. Additional correlations suggest that flanking residues act in concert with the GxxxG motif, and that size complementarity is maintained at the interface, consistent with the idea that the identified sequence patterns represent packing motifs. The convergent identification of similar sequence patterns from an analysis of the transmembrane domains in the SwissProt sequence database suggests that these packing motifs are frequently utilized in naturally occurring helical membrane proteins. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)911-919
Number of pages9
JournalJournal of Molecular Biology
Issue number3
StatePublished - Feb 25 2000


  • Association
  • Glycine
  • Membrane protein
  • Protein folding

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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