title: Structural basis for a novel interaction between TXNIP and Vav2.
abstract: Thioredoxin-interacting protein (TXNIP) is a multifunctional protein involved in diverse cellular processes such as cell proliferation and apoptosis. TXNIP stability is controlled by the ubiquitin-proteasome pathway, and the E3 ubiquitin ligase Itch directly interacts with TXNIP via PPxY motifs of TXNIP. In a previously published study, we have shown that phosphorylation of the PPxY tyrosyl residue switches TXNIP selectivity between different binding partners. Here, we describe that tyrosine-phosphorylated PPxY motifs also bind to SH2 domains of Vav2 and Src with dissociation constants around 10 μm and that phosphorylation is indispensable for these interactions as well. The crystal structure of the complex between a phosphorylated PPxY motif, and the SH2 domain of Vav2 reveals a conserved recognition mechanism.
authors.affiliation: Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Science, Central China Normal University, Wuhan, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Liu
authors.affiliation: Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Science, Central China Normal University, Wuhan, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Wu
authors.affiliation: China-Japan Union Hospital of Jilin University, Changchun, China.
authors.forename: Minru
authors.initials: M
authors.lastname: Zong
authors.affiliation: Structural Genomics Consortium, University of Toronto, Ontario, Canada.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Tempel
authors.affiliation: Structural Genomics Consortium, University of Toronto, Ontario, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Loppnau
authors.affiliation: Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Science, Central China Normal University, Wuhan, China.|Structural Genomics Consortium, University of Toronto, Ontario, Canada.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010766:Phosphorylation; D054730:Protein Interaction Domains and Motifs; D051567:Proto-Oncogene Proteins c-vav / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity; D014443:Tyrosine / Q000737:chemistry; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D018909:src Homology Domains
chemical_list: D002352:Carrier Proteins; D051567:Proto-Oncogene Proteins c-vav; D011994:Recombinant Proteins; D012097:Repressor Proteins; C486715:TXNIP protein, human; C093651:VAV2 protein, human; D014443:Tyrosine; C432966:ITCH protein, human; D044767:Ubiquitin-Protein Ligases
keywords: SH2 domain; TXNIP; Tyrosine-phosphorylated PPxY motif; Vav2