7awa | pdb_00007awa
SctV (SsaV) cytoplasmic domain
Structural highlights
Function[SSAV_SALTY] Component of Salmonella pathogenicity island 2 (SPI-2) type III secretion system, required for secretion of some type III-secreted effectors including the SpvB toxin.[1] Publication Abstract from PubMedBacterial 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. Structure of the cytoplasmic domain of SctV (SsaV) from the Salmonella SPI-2 injectisome and implications for a pH sensing mechanism.,Matthews-Palmer TRS, Gonzalez-Rodriguez N, Calcraft T, Lagercrantz S, Zachs T, Yu XJ, Grabe GJ, Holden DW, Nans A, Rosenthal PB, Rouse SL, Beeby M J Struct Biol. 2021 Mar 26;213(2):107729. doi: 10.1016/j.jsb.2021.107729. PMID:33774138[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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