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Structural Details of Human Tuba Recruitment by InlC of Listeria monocytogenes Elucidate Bacterial Cell-Cell Spreading

2013; Elsevier BV; Volume: 22; Issue: 2 Linguagem: Inglês

10.1016/j.str.2013.10.017

1878-4186

Lilia Polle, Luciano A. Rigano, Rowan Julian, Keith Ireton, Wolf‐Dieter Schubert,

Microbial Inactivation Methods

Highlights•Physiological complexes of human adapter protein Tuba with N-WASP and Mena•Infection-related complex of listerial InlC with Tuba SH3-6•Molecular details of N-WASP displacement from Tuba SH3-6 by InlC•Disruption of InlC function in vivo and in vitro by a single amino acids exchangeSummaryThe 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 SH3 domain (SH3-6) 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 SH3-6 with physiological partners N-WASP and Mena reveal equivalent binding modes but distinct affinities. The interaction surface of the infection complex InlC/Tuba SH3-6 is centered on phenylalanine 146 of InlC stacking upon asparagine 1569 of Tuba. Replacing Phe146 by alanine largely abrogates molecular affinity and in 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.Graphical abstract