title: A common structural motif in the binding of virulence factors to bacterial secretion chaperones.
abstract: Salmonella invasion protein A (SipA) is translocated into host cells by a type III secretion system (T3SS) and comprises two regions: one domain binds its cognate type III secretion chaperone, InvB, in the bacterium to facilitate translocation, while a second domain functions in the host cell, contributing to bacterial uptake by polymerizing actin. We present here the crystal structures of the SipA chaperone binding domain (CBD) alone and in complex with InvB. The SipA CBD is found to consist of a nonglobular polypeptide as well as a large globular domain, both of which are necessary for binding to InvB. We also identify a structural motif that may direct virulence factors to their cognate chaperones in a diverse range of pathogenic bacteria. Disruption of this structural motif leads to a destabilization of several chaperone-substrate complexes from different species, as well as an impairment of secretion in Salmonella.
authors.affiliation: Laboratory of Structural Microbiology, The Rockefeller University, New York, New York 10021, USA.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Lilic
authors.forename: Milos
authors.initials: M
authors.lastname: Vujanac
authors.forename: C Erec
authors.initials: CE
authors.lastname: Stebbins
mesh_terms: D020816:Amino Acid Motifs / Q000502:physiology; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D018360:Crystallography, X-Ray; D018390:Gene Targeting; D008840:Microfilament Proteins / Q000737:chemistry* / Q000502:physiology; D018832:Molecular Chaperones / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary; D012486:Salmonella typhimurium / Q000737:chemistry / Q000502:physiology; D037521:Virulence Factors / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D008840:Microfilament Proteins; D018832:Molecular Chaperones; C118287:SipA protein, Salmonella; D037521:Virulence Factors; C088597:invB protein, Salmonella