Maintenance of an unfolded polypeptide by a cognate chaperone in bacterial type III secretion.
Many bacterial pathogens use a type III protein secretion system to deliver virulence effector proteins directly into the host cell cytosol, where they modulate cellular processes. A requirement for the effective translocation of several such effector proteins is the binding of specific cytosolic chaperones, which typically interact with discrete domains in the virulence factors. We report here the crystal structure at 1.9 A resolution of the chaperone-binding domain of the Salmonella effector protein SptP with its cognate chaperone SicP. The structure reveals that this domain is maintained in an extended, unfolded conformation that is wound around three successive chaperone molecules. Short segments from two different SptP molecules are juxtaposed by the chaperones, where they dimerize across a hydrophobic interface. These results imply that the chaperones associated with the type III secretion system maintain their substrates in a secretion-competent state that is capable of engaging the secretion machinery to travel through the type III apparatus in an unfolded or partially folded manner.
Stebbins
C E
CE
Section of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale School of Medicine, New Haven, Connecticut 06336, USA.
Galán
J E
JE
D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D018833:Chaperonins / Q000378:metabolism*; D018360:Crystallography, X-Ray; D020690:GTPase-Activating Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D012486:Salmonella typhimurium / Q000378:metabolism* / Q000472:pathogenicity; D014774:Virulence
D001426:Bacterial Proteins; D020690:GTPase-Activating Proteins; D011993:Recombinant Fusion Proteins; C097739:SIC protein, Streptococcus; D017027:Protein Tyrosine Phosphatases; C439890:sptP protein, Salmonella typhimurium; D018833:Chaperonins