2lnh
From Proteopedia
Enterohaemorrhagic E. coli (EHEC) exploits a tryptophan switch to hijack host F-actin assembly
Structural highlights
Function[WASL_HUMAN] Regulates actin polymerization by stimulating the actin-nucleating activity of the Arp2/3 complex. Binds to HSF1/HSTF1 and forms a complex on heat shock promoter elements (HSE) that negatively regulates HSP90 expression.[1] [ESFU3_ECO57] Required for efficient pedestal formation in host epithelial cells during infection. Acts as an intermediate between Tir (via host BAIAP2) and host WASL/N-WASP. Directly binds and activates WASL/N-WASP, which stimulates actin polymerization and leads to the formation of actin pedestals at the sites of bacterial adhesion.[2] [3] [BI2L1_HUMAN] May function as adapter protein. Involved in the formation of clusters of actin bundles. Plays a role in the reorganization of the actin cytoskeleton in response to bacterial infection.[4] [5] [6] Publication Abstract from PubMedIntrinsically disordered protein (IDP)-mediated interactions are often characterized by low affinity but high specificity. These traits are essential in signaling and regulation that require reversibility. Enterohaemorrhagic Escherichia coli (EHEC) exploit this situation by commandeering host cytoskeletal signaling to stimulate actin assembly beneath bound bacteria, generating "pedestals" that promote intestinal colonization. EHEC translocates two proteins, EspF(U) and Tir, which form a complex with the host protein IRTKS. The interaction of this complex with N-WASP triggers localized actin polymerization. We show that EspF(U) is an IDP that contains a transiently alpha-helical N-terminus and dynamic C-terminus. Our structure shows that single EspF(U) repeat forms a high-affinity trimolecular complex with N-WASP and IRTKS. We demonstrate that bacterial and cellular ligands interact with IRTKS SH3 in a similar fashion, but the bacterial protein has evolved to outcompete cellular targets by utilizing a tryptophan switch that offers superior binding affinity enabling EHEC-induced pedestal formation. Enterohaemorrhagic Escherichia Coli Exploits a Tryptophan Switch to Hijack Host F-Actin Assembly.,Aitio O, Hellman M, Skehan B, Kesti T, Leong JM, Saksela K, Permi P Structure. 2012 Aug 21. PMID:22921828[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||
