Structural analysis of a rhomboid family intramembrane protease reveals a gating mechanism for substrate entry

Zhuoru Wu, Nieng Yan, Liang Feng, Adam Oberstein, Hanchi Yan, Rosanna P. Baker, Lichuan Gu, Philip D. Jeffrey, Sinisa Urban, Yigong Shi

Research output: Contribution to journalArticle

185 Scopus citations

Abstract

Intramembrane proteolysis regulates diverse biological processes. Cleavage of substrate peptide bonds within the membrane bilayer is catalyzed by integral membrane proteases. Here we report the crystal structure of the transmembrane core domain of GlpG, a rhomboid-family intramembrane serine protease from Escherichia coli. The protein contains six transmembrane helices, with the catalytic Ser201 located at the N terminus of helix α4 approximately 10 Å below the membrane surface. Access to water molecules is provided by a central cavity that opens to the extracellular region and converges on Ser201. One of the two GlpG molecules in the asymmetric unit has an open conformation at the active site, with the transmembrane helix α5 bent away from the rest of the molecule. Structural analysis suggests that substrate entry to the active site is probably gated by the movement of helix α5.

Original languageEnglish (US)
Pages (from-to)1084-1091
Number of pages8
JournalNature Structural and Molecular Biology
Volume13
Issue number12
DOIs
StatePublished - Dec 11 2006

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

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    Wu, Z., Yan, N., Feng, L., Oberstein, A., Yan, H., Baker, R. P., Gu, L., Jeffrey, P. D., Urban, S., & Shi, Y. (2006). Structural analysis of a rhomboid family intramembrane protease reveals a gating mechanism for substrate entry. Nature Structural and Molecular Biology, 13(12), 1084-1091. https://doi.org/10.1038/nsmb1179