Maintenance of an unfolded polypeptide by a cognate chaperone in bacterialtype III secretion

Many bacterial pathogens use a type III protein secretion system to deliver virulence effector proteins directly into the host cell cytosol, where the y modulate cellular processes(1,2). A requirement for the effective translo cation of several such effector proteins is the binding of specific cytosol ic chaperones, which typically interact with discrete domains in the virule nce factors(3,4,5). We report here the crystal structure at 1.9 Angstrom re solution of the chaperone-binding domain of the Salmonella effector protein SptP with its cognate chaperone SicP. The structure reveals that this doma in is maintained in an extended, unfolded conformation that is wound around three successive chaperone molecules. Short segments from two different Sp tP 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 tra vel through the type III apparatus in an unfolded or partially folded manne r.