2rrf | pdb_00002rrf

The solution structure of the C-terminal region of Zinc finger FYVE domain-containing protein 21

spinqualitylabelsall models 2rrf, 20 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2rrf is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ZFY21_HUMAN] Plays a role in cell adhesion, and thereby in cell motility which requires repeated formation and disassembly of focal adhesions. Regulates microtubule-induced PTK2/FAK1 dephosphorylation, an event important for focal adhesion disassembly, as well as integrin beta-1/ITGB1 cell surface expression. Publication Abstract from PubMed Directional migration of adherent cells on an extracellular matrix requires repeated formation and disassembly of focal adhesions (FAs). We have identified ZF21 as a regulator of disassembly of FAs and cell migration, and increased expression of the gene has been linked to metastatic colon cancer. ZF21 is a member of a protein family characterized by the presence of the FYVE domain, which is conserved among Fab1p, YOPB, Vps27p, and EEA1 proteins, and has been shown to mediate the binding of such proteins to phosphoinositides in the lipid layers of cell membranes. ZF21 binds multiple factors that promote disassembly of FAs such as FAK, beta-tubulin, m-calpain, and SHP-2. ZF21 does not contain any other known protein motifs other than the FYVE domain, but a region of the protein C terminal to the FYVE domain is sufficient to mediate binding to beta-tubulin. In this study, we demonstrate that the C-terminal region is important for the ability of ZF21 to induce disassembly of FAs and cell migration, and to promote an early step of experimental metastasis to the lung in mice. In the light of the importance of the C-terminal region, we analyzed its ternary structure using NMR spectroscopy. We demonstrate that this region exhibits a structure similar to that of a canonical pleckstrin homology (PH) domain, but that it lacks a positively charged interface to bind phosphatidylinositol phosphate. Thus, ZF21 contains a novel non-canonical PH-like domain that is a possible target to develop a therapeutic strategy to treat metastatic cancer. ZF21, a regulator of the disassembly of focal adhesions and cancer metastasis contains a novel non-canonical pleckstrin homology domain.,Nagano M, Hoshino D, Koshiba S, Shuo T, Koshikawa N, Tomizawa T, Hayashi F, Tochio N, Harada T, Akizawa T, Watanabe S, Handa N, Shirouzu M, Kigawa T, Yokoyama S, Seiki M J Biol Chem. 2011 Jul 15. PMID:21768110 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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