Mathieu Botte, Nathan 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, and
Christiane Schaffitzel.
A central cavity within the holo-translocon suggests a mechanism for
membrane protein insertion.
Scientific Reports, 6:38399, 2016.
(PMC: PMC5141469)
BOTT2016
The universally conserved SecY-complex transports proteins into and across cell membranes 1,2. In bacteria, SecYEG, SecDF, YajC and YidC constitute the holo-translocon (HTL), with the capability for both protein-secretion and membrane protein insertion 3-6. Here, we present the architecture of the HTL by employing an integrated approach combining new data gathered by electron cryo-microscopy, small-angle neutron scattering (SANS) and a biochemical analysis. The results guided the placement of the existing x-ray structures of the individual components of the HTL to obtain a quasi-atomic model of the super-complex. Their arrangement around a central lipid-containing pool reveals a compelling and unexpected 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 polypeptide. The lateral gate of SecY for membrane insertion is adjacent to the membrane ‘insertase’ YidC. Absolute scale SANS employing a novel contrast match point analysis revealed a dynamic complex that can adopt open and compact configurations around an adaptable central lipid-filled chamber, wherein polytopic membrane proteins could fold, sheltered from aggregation and proteolysis. Our results uncover a highly mobile HTL complex capable of flexibly adapting its geometry and local environment according to the requirements of the inserting membrane protein substrate, reminiscent of the process of assisted folding for soluble proteins.
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