5ke1

From Proteopedia

Structure of a C-terminal fragment of the IcsA/VirG passenger-domain

Structural highlights

5ke1 is a 2 chain structure with sequence from Shigella flexneri. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.9Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ICSA_SHIFL Essential for bacterial spreading by eliciting polar deposition of filamentous actin (actin-based motility). Inside the host cell mediates nucleation and polymerization of actin molecules on the bacterial surface, which provides the propulsive force for intracellular movement and intercellular dissemination of the bacterium. During invasion of mammalian cells, triggers autophagy by binding to APG5L. Interaction with IcsB leads to escape from the autophagic host defense system. Also binds ATP and displays weak ATPase activity.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

IcsA/VirG is a key virulence factor of the human pathogen Shigella flexneri, acting as both an adhesin and actin-polymerizing factor during infection. We identified a soluble expression construct of the IcsA/VirG alpha-domain using the ESPRIT library screening system and determined its structure to 1.9A resolution. In addition to the previously characterized autochaperone domain, our structure reveals a new domain, which shares a common fold with the autochaperone domains of various autotransporters. We further provide insight into the previously structurally uncharacterized beta-helix domain that harbors the polar targeting motif and passenger-associated transport repeat. This structure is the first of any member of the recently identified passenger-associated transport repeat-containing autotransporters. Thus, it provides new insights into the overall architecture of this class of autotransporters, the function of the identified additional autochaperone domain and the structural properties of motifs involved in polar targeting and secretion of the Shigella flexneri virulence factor IcsA/VirG.

Structural insights into the architecture of the Shigella flexneri virulence factor IcsA/VirG and motifs involved in polar distribution and secretion.,Leupold S, Busing P, Mas PJ, Hart DJ, Scrima A J Struct Biol. 2017 Mar 6. pii: S1047-8477(17)30037-0. doi:, 10.1016/j.jsb.2017.03.003. PMID:28268178^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Fukuda I, Suzuki T, Munakata H, Hayashi N, Katayama E, Yoshikawa M, Sasakawa C. Cleavage of Shigella surface protein VirG occurs at a specific site, but the secretion is not essential for intracellular spreading. J Bacteriol. 1995 Apr;177(7):1719-26. PMID:7896693
↑ Bernardini ML, Mounier J, d'Hauteville H, Coquis-Rondon M, Sansonetti PJ. Identification of icsA, a plasmid locus of Shigella flexneri that governs bacterial intra- and intercellular spread through interaction with F-actin. Proc Natl Acad Sci U S A. 1989 May;86(10):3867-71. PMID:2542950
↑ d'Hauteville H, Sansonetti PJ. Phosphorylation of IcsA by cAMP-dependent protein kinase and its effect on intracellular spread of Shigella flexneri. Mol Microbiol. 1992 Apr;6(7):833-41. PMID:1602963
↑ Suzuki T, Miki H, Takenawa T, Sasakawa C. Neural Wiskott-Aldrich syndrome protein is implicated in the actin-based motility of Shigella flexneri. EMBO J. 1998 May 15;17(10):2767-76. PMID:9582270 doi:10.1093/emboj/17.10.2767
↑ Ogawa M, Yoshimori T, Suzuki T, Sagara H, Mizushima N, Sasakawa C. Escape of intracellular Shigella from autophagy. Science. 2005 Feb 4;307(5710):727-31. Epub 2004 Dec 2. PMID:15576571 doi:10.1126/science.1106036
↑ Leupold S, Busing P, Mas PJ, Hart DJ, Scrima A. Structural insights into the architecture of the Shigella flexneri virulence factor IcsA/VirG and motifs involved in polar distribution and secretion. J Struct Biol. 2017 Mar 6. pii: S1047-8477(17)30037-0. doi:, 10.1016/j.jsb.2017.03.003. PMID:28268178 doi:http://dx.doi.org/10.1016/j.jsb.2017.03.003