A central cavity within the holo-translocon suggests a mechanism for membrane protein insertion

Mathieu Botte, Nathan R. Zaccai, Jelger Lycklama À. Nijeholt, Remy Martin, Kèvin Knoops, Gabor Papai, Juan Zou, Aurélien Deniaud, Manikandan Karuppasamy, Qiyang Jiang, Abhishek Singha Roy, Klaus Schulten, Patrick Schultz, Juri Rappsilber, Giuseppe Zaccai, Imre Berger, Ian Collinson, Christiane Schaffitzel

Research output: Contribution to journalArticle

Abstract

The conserved SecYEG protein-conducting channel and the accessory proteins SecDF-YajC and YidC constitute the bacterial holo-translocon (HTL), capable of protein-secretion and membrane-protein insertion. By employing an integrative approach combining small-angle neutron scattering (SANS), low-resolution electron microscopy and biophysical analyses we determined the arrangement of the proteins and lipids within the super-complex. The results guided the placement of X-ray structures of individual HTL components and allowed the proposal of a model of the functional translocon. Their arrangement around a central lipid-containing pool conveys an unexpected, but compelling mechanism for membrane-protein insertion. The periplasmic domains of YidC and SecD are poised at the protein-channel exit-site of SecY, presumably to aid the emergence of translocating polypeptides. The SecY lateral gate for membrane-insertion is adjacent to the membrane-insertase' YidC. Absolute-scale SANS employing a novel contrast-match-point analysis revealed a dynamic complex adopting open and compact configurations around an adaptable central lipid-filled chamber, wherein polytopic membrane-proteins could fold, sheltered from aggregation and proteolysis.

Original languageEnglish (US)
Article number38399
JournalScientific reports
Volume6
DOIs
StatePublished - Dec 7 2016

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Membrane Proteins
Small Angle Scattering
Neutrons
Proteins
Lipids
Membranes
Proteolysis
Electron Microscopy
X-Rays
Peptides

ASJC Scopus subject areas

  • General

Cite this

Botte, M., Zaccai, N. R., Nijeholt, J. L. À., Martin, R., Knoops, K., Papai, G., ... Schaffitzel, C. (2016). A central cavity within the holo-translocon suggests a mechanism for membrane protein insertion. Scientific reports, 6, [38399]. https://doi.org/10.1038/srep38399

A central cavity within the holo-translocon suggests a mechanism for membrane protein insertion. / Botte, Mathieu; Zaccai, Nathan R.; Nijeholt, Jelger Lycklama À.; Martin, Remy; Knoops, Kèvin; Papai, Gabor; Zou, Juan; Deniaud, Aurélien; Karuppasamy, Manikandan; Jiang, Qiyang; Roy, Abhishek Singha; Schulten, Klaus; Schultz, Patrick; Rappsilber, Juri; Zaccai, Giuseppe; Berger, Imre; Collinson, Ian; Schaffitzel, Christiane.

In: Scientific reports, Vol. 6, 38399, 07.12.2016.

Research output: Contribution to journalArticle

Botte, M, Zaccai, NR, Nijeholt, JLÀ, Martin, R, Knoops, K, Papai, G, Zou, J, Deniaud, A, Karuppasamy, M, Jiang, Q, Roy, AS, Schulten, K, Schultz, P, Rappsilber, J, Zaccai, G, Berger, I, Collinson, I & Schaffitzel, C 2016, 'A central cavity within the holo-translocon suggests a mechanism for membrane protein insertion', Scientific reports, vol. 6, 38399. https://doi.org/10.1038/srep38399
Botte, Mathieu ; Zaccai, Nathan R. ; Nijeholt, Jelger Lycklama À. ; Martin, Remy ; Knoops, Kèvin ; Papai, Gabor ; Zou, Juan ; Deniaud, Aurélien ; Karuppasamy, Manikandan ; Jiang, Qiyang ; Roy, Abhishek Singha ; Schulten, Klaus ; Schultz, Patrick ; Rappsilber, Juri ; Zaccai, Giuseppe ; Berger, Imre ; Collinson, Ian ; Schaffitzel, Christiane. / A central cavity within the holo-translocon suggests a mechanism for membrane protein insertion. In: Scientific reports. 2016 ; Vol. 6.
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