3tul | pdb_00003tul
Crystal structure of N-terminal region of Type III Secretion Major Translocator SipB (residues 82-226)
Structural highlights
Function[SIPB_SALTY] Required for entry into the host cell through presentation or delivery of SipC at the host cell plasma membrane. Along with SipC, is necessary for the transfer of other effector proteins into the host cell. Induces macrophage apoptosis either by binding and activating the proapoptotic enzyme caspase-1 (caspase-1 dependent), resulting in the release of interleukin-1 beta active form, or by disrupting mitochondria and inducing autophagy (caspase-1 independent). The former is dependent of its membrane-fusion activity. The SipBC complex, in association with its chaperone SicA, is regulated by binding of InvE.[1] [2] Publication Abstract from PubMedMany pathogenic Gram-negative bacteria utilize type III secretion systems (T3SSs) to alter the normal functions of target cells. Shigella flexneri uses its T3SS to invade human intestinal cells to cause bacillary dysentery (shigellosis) that is responsible for over one million deaths per year. The Shigella type III secretion apparatus is composed of a basal body spanning both bacterial membranes and an exposed oligomeric needle. Host altering effectors are secreted through this energized unidirectional conduit to promote bacterial invasion. The active needle tip complex of S. flexneri is composed of a tip protein, IpaD, and two pore-forming translocators, IpaB and IpaC. While the atomic structure of IpaD has been elucidated and studied, structural data on the hydrophobic translocators from the T3SS family remain elusive. We present here the crystal structures of a protease-stable fragment identified within the N-terminal regions of IpaB from S. flexneri and SipB from Salmonella enterica serovar Typhimurium determined at 2.1 A and 2.8 A limiting resolution, respectively. These newly identified domains are composed of extended-length (114 A in IpaB and 71 A in SipB) coiled-coil motifs that display a high degree of structural homology to one another despite the fact that they share only 21% sequence identity. Further structural comparisons also reveal substantial similarity to the coiled-coil regions of pore-forming proteins from other Gram-negative pathogens, notably, colicin Ia. This suggests that these mechanistically separate and functionally distinct membrane-targeting proteins may have diverged from a common ancestor during the course of pathogen-specific evolutionary events. The Structures of Coiled-Coil Domains from Type III Secretion System Translocators Reveal Homology to Pore-Forming Toxins.,Barta ML, Dickenson NE, Patil M, Keightley A, Wyckoff GJ, Picking WD, Picking WL, Geisbrecht BV J Mol Biol. 2012 Feb 1. PMID:22321794[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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