Structural Basis for Signal-Sequence Recognition by the Translocase Motor SecA as Determined by NMR

Ioannis Gelis, Alexandre M.J.J. Bonvin, Dimitra Keramisanou, Marina Koukaki, Giorgos Gouridis, Spyridoula Karamanou, Anastassios Economou, Charalampos G. Kalodimos

Research output: Contribution to journalArticlepeer-review

343 Scopus citations


Recognition of signal sequences by cognate receptors controls the entry of virtually all proteins to export pathways. Despite its importance, this process remains poorly understood. Here, we present the solution structure of a signal peptide bound to SecA, the 204 kDa ATPase motor of the Sec translocase. Upon encounter, the signal peptide forms an α-helix that inserts into a flexible and elongated groove in SecA. The mode of binding is bimodal, with both hydrophobic and electrostatic interactions mediating recognition. The same groove is used by SecA to recognize a diverse set of signal sequences. Impairment of the signal-peptide binding to SecA results in significant translocation defects. The C-terminal tail of SecA occludes the groove and inhibits signal-peptide binding, but autoinhibition is relieved by the SecB chaperone. Finally, it is shown that SecA interconverts between two conformations in solution, suggesting a simple mechanism for polypeptide translocation.

Original languageEnglish (US)
Pages (from-to)756-769
Number of pages14
Issue number4
StatePublished - Nov 16 2007
Externally publishedYes

Bibliographical note

Funding Information:
We are grateful to B. Pozidis for the MALLS data, S. Backo and O. Uchime for assistance with sample preparation, and R. Ghose for useful discussions. This work was supported by U.S. National Institutes of Health grant GM-73854 (to C.G.K.), by a Scientist Development Grant from the American Heart Association (to C.G.K.), and by the European Union (grant LSHG-CT-2005-037586 to A.E.) and the Greek General Secretariat of Research and the European Regional Development Fund (grants 01AKMON46 and PENED03ED623 to A.E.). G.G. is an Onassis Foundation predoctoral fellow.




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