Structural details of human tuba recruitment by InlC of Listeria monocytogenes elucidate bacterial cell-cell spreading.

[wiskott-aldrich syndrome]

The human pathogen Listeria monocytogenes is able to directly spread to neighboring cells of host tissues , a process recently linked to the virulence factor InlC . InlC targets the sixth SH 3 domain (SH 3 -6 ) of human Tuba , disrupting its physiological interaction with the cytoskeletal protein N-WASP . The resulting loss of cortical actin tension may slacken the junctional membrane , allowing protrusion formation by motile Listeria . Complexes of Tuba SH 3 -6 with physiological partners N-WASP and Mena reveal equivalent binding modes but distinct affinities . The interaction surface of the infection complex InlC /Tuba SH 3 -6 is centered on phenylalanine 146 of InlC stacking upon asparagine 1569 of Tuba . Replacing Phe 146 by alanine largely abrogates molecular affinity and in Â vivo mimics deletion of inlC . Collectively , our findings indicate that InlC hijacks Tuba through its LRR domain , blocking the peptide binding groove to prevent recruitment of its physiological partners .