1nty

Crystal structure of the first DH/PH domain of Trio to 1.7 A

spinqualitylabelsall models 1nty, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1nty is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Gene: TRIO (Homo sapiens) Resources: FirstGlance, OCA, RCSB, PDBsum Function [TRIO_HUMAN] Promotes the exchange of GDP by GTP. Together with leukocyte antigen-related (LAR) protein, it could play a role in coordinating cell-matrix and cytoskeletal rearrangements necessary for cell migration and cell growth. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The multidomain protein Trio regulates among others neuronal outgrowth and axonal guidance in vertebrates and invertebrates. Trio contains two Dbl-homology/pleckstrin homology (DH/PH) tandem domains that activate several RhoGTPases. Here, we present the x-ray structure of the N-terminal DH/PH, hereafter TrioN, refined to 1.7-A resolution. We show that the relative orientations of the DH and PH domains of TrioN and free Dbs are similar. However, this relative orientation is dissimilar to Dbs in the Dbs/Cdc42 structure. In vitro nucleotide exchange experiments catalyzed by TrioN show that RhoG is approximately 3x more efficiently exchanged than Rac and support the conclusion that RhoG is likely the downstream target of TrioN. Residues 54 and 69, which are not conserved between the two GTPases, are responsible for this specificity. Dot-blot assay reveals that the TrioN-PH domain does not detectably bind phosphatidylinositol 3,4-bisphosphate, PtdIns(3,4)P(2), or other phospholipids. This finding is supported by our three-dimensional structure and affinity binding experiments. Interestingly, the presence of RhoG but not Rac or a C-terminal-truncated RhoG mutant allows TrioN to bind PtdIns(3,4)P(2) with a micromolar affinity constant. We conclude the variable C-terminal basic tail of RhoG specifically assists the recruitment of the TrioN-PH domain to specific membrane-bound phospholipids. Our data suggest a role for the phosphoinositide 3-kinase, PI 3-kinase, in modulating the Trio/RhoG signaling pathway. The C-terminal basic tail of RhoG assists the guanine nucleotide exchange factor trio in binding to phospholipids.,Skowronek KR, Guo F, Zheng Y, Nassar N J Biol Chem. 2004 Sep 3;279(36):37895-907. Epub 2004 Jun 15. PMID:15199069 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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