Imperial College London
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DrMorganBeeby

Faculty of Natural Sciences, Department of Life Sciences

Reader in Structural Biology
 
 
 
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m.beeby Website

 
 
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Location

 

502Sir Ernst Chain BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Matthews-Palmer:2021:10.1016/j.jsb.2021.107729,
author = {Matthews-Palmer, T and Gonzalez-Rodriguez, N and Calcraft, T and Lagercrantz, S and Zachs, T and Yu, X and Grabe, G and Holden, D and Nans, A and Rosenthal, P and Rouse, S and Beeby, M},
doi = {10.1016/j.jsb.2021.107729},
journal = {Journal of Structural Biology},
title = {Structure of the cytoplasmic domain of SctV (SsaV) from the Salmonella SPI-2 injectisome and implications for a pH sensing mechanism},
url = {http://dx.doi.org/10.1016/j.jsb.2021.107729},
volume = {213},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Bacterial type III secretion systems assemble the axial structures of both injectisomes and flagella. Injectisome type III secretion systems subsequently secrete effector proteins through their hollow needle into a host, requiring co-ordination. In the Salmonella enterica serovar Typhimurium SPI-2 injectisome, this switch is triggered by sensing the neutral pH of the host cytoplasm. Central to specificity switching is a nonameric SctV protein with an N-terminal transmembrane domain and a toroidal C-terminal cytoplasmic domain. A ‘gatekeeper’ complex interacts with the SctV cytoplasmic domain in a pH dependent manner, facilitating translocon secretion while repressing effector secretion through a poorly understood mechanism. To better understand the role of SctV in SPI-2 translocon-effector specificity switching, we purified full-length SctV and determined its toroidal cytoplasmic region’s structure using cryo-EM. Structural comparisons and molecular dynamics simulations revealed that the cytoplasmic torus is stabilized by its core subdomain 3, about which subdomains 2 and 4 hinge, varying the flexible outside cleft implicated in gatekeeper and substrate binding. In light of patterns of surface conservation, deprotonation, and structural motion, the location of previously identified critical residues suggest that gatekeeper binds a cleft buried between neighboring subdomain 4s. Simulations suggest that a local pH change from 5 to 7.2 stabilizes the subdomain 3 hinge and narrows the central aperture of the nonameric torus. Our results are consistent with a model of local pH sensing at SctV, where pH-dependent dynamics of SctV cytoplasmic domain affect binding of gatekeeper complex.
AU  - Matthews-Palmer,T
AU  - Gonzalez-Rodriguez,N
AU  - Calcraft,T
AU  - Lagercrantz,S
AU  - Zachs,T
AU  - Yu,X
AU  - Grabe,G
AU  - Holden,D
AU  - Nans,A
AU  - Rosenthal,P
AU  - Rouse,S
AU  - Beeby,M
DO  - 10.1016/j.jsb.2021.107729
PY  - 2021///
SN  - 1047-8477
TI  - Structure of the cytoplasmic domain of SctV (SsaV) from the Salmonella SPI-2 injectisome and implications for a pH sensing mechanism
T2  - Journal of Structural Biology
UR  - http://dx.doi.org/10.1016/j.jsb.2021.107729
UR  - http://hdl.handle.net/10044/1/89027
VL  - 213
ER  -
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