title: Crystal structure of human Intersectin-2L C2 domain.
abstract: Intersectin-2L (ITSN-2L) is a long isoform of ITSN family, which is a multimodule scaffolding protein functioning in membrane-associated molecular trafficking and signal transduction pathways. ITSN-2L possesses a carboxy-terminal extension encoding a Dbl homology domain (DH), a pleckstrin homology domain (PH) and a C2 domain, suggesting that it could act as a guanine nucleotide exchange factor for Rho-like GTPases. But the role of C2 domain is obscure in this process. Here we report the crystal structure of human ITSN-2L C2 domain at 1.56Å resolution. The sequence and structural alignment of ITSN-2L C2 domain with other members of C2 domain protein family indicate its vital cellular roles in membrane trafficking, the generation of lipid-second messengers and activation of GTPases. Moreover, our data show the possible roles of ITSN-2L C2 domain in regulating the activity of Cdc42.
authors.affiliation: Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Science, Huazhong Normal University, Wuhan 430079, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Shen
authors.forename: Guomei
authors.initials: G
authors.lastname: Xiong
authors.forename: Yahong
authors.initials: Y
authors.lastname: Guo
authors.forename: Lingfu
authors.initials: L
authors.lastname: Deng
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.forename: Jihong
authors.initials: J
authors.lastname: Yang
authors.forename: Chao
authors.initials: C
authors.lastname: Qi
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000737:chemistry* / Q000378:metabolism*; D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000378:metabolism; D018360:Crystallography, X-Ray; D004789:Enzyme Activation; D006801:Humans; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C509776:ITSN2 protein, human; D026901:Membrane Transport Proteins; D020764:cdc42 GTP-Binding Protein