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

doi:10.1016/j.cell.2007.09.039

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 journal › Article › peer-review

346 Scopus citations

Abstract

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 language	English (US)
Pages (from-to)	756-769
Number of pages	14
Journal	Cell
Volume	131
Issue number	4
DOIs	https://doi.org/10.1016/j.cell.2007.09.039
State	Published - Nov 16 2007
Externally published	Yes

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.

Keywords

CELLBIO
PROTEINS

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title = "Structural Basis for Signal-Sequence Recognition by the Translocase Motor SecA as Determined by NMR",

abstract = "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.",

keywords = "CELLBIO, PROTEINS",

author = "Ioannis Gelis and Bonvin, {Alexandre M.J.J.} and Dimitra Keramisanou and Marina Koukaki and Giorgos Gouridis and Spyridoula Karamanou and Anastassios Economou and Kalodimos, {Charalampos G.}",

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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AU - Gelis, Ioannis

AU - Bonvin, Alexandre M.J.J.

AU - Keramisanou, Dimitra

AU - Koukaki, Marina

AU - Gouridis, Giorgos

AU - Karamanou, Spyridoula

AU - Economou, Anastassios

AU - Kalodimos, Charalampos G.

N1 - 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.

PY - 2007/11/16

Y1 - 2007/11/16

N2 - 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.

AB - 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.

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KW - PROTEINS

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

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