Structure of the mycobacterial ESX-5 type VII secretion system pore complex

被引：37

作者：

Beckham, Katherine S. H. ^{[1
]}

Ritter, Christina ^{[1
]}

Chojnowski, Grzegorz ^{[1
]}

Ziemianowicz, Daniel S. ^{[1
]}

Mullapudi, Edukondalu ^{[1
]}

Rettel, Mandy ^{[2
]}

Savitski, Mikhail M. ^{[2
]}

Mortensen, Simon A. ^{[1
]}

Kosinski, Jan ^{[1
,3
,4
]}

Wilmanns, Matthias ^{[1
,5
]}

机构：

[1] European Mol Biol Lab, Hamburg Unit, Notkestr 85, D-22607 Hamburg, Germany

[2] European Mol Biol Lab, Heidelberg, Germany

[3] Ctr Struct Syst Biol CSSB, Hamburg, Germany

[4] European Mol Biol Lab, Struct & Computat Biol Unit, Meyerhofstr 1, D-69117 Heidelberg, Germany

[5] Univ Hamburg Clin Ctr Hamburg Eppendorf, Martinistr 52, D-20246 Hamburg, Germany

来源：

SCIENCE ADVANCES | 2021年 / 7卷 / 26期

关键词：

CRYO-EM; VISUALIZATION; ARCHITECTURE; REFINEMENT; VIRULENCE;

D O I：

10.1126/sciadv.abg9923

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The ESX-5 type VII secretion system is a membrane-spanning protein complex key to the virulence of mycobacterial pathogens. However, the overall architecture of the fully assembled translocation machinery and the composition of the central secretion pore have remained unknown. Here, we present the high-resolution structure of the 2.1-megadalton ESX-5 core complex. Our structure captured a dynamic, secretion-competent conformation of the pore within a well-defined transmembrane section, sandwiched between two flexible protein layers at the cytosolic entrance and the periplasmic exit. We propose that this flexibility endows the ESX-5 machinery with large conformational plasticity required to accommodate targeted protein secretion. Compared to known secretion systems, a highly dynamic state of the pore may represent a fundamental principle of bacterial secretion machineries.

引用

页数：10

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