4xh2

Crystal structure of human paxillin LD4 motif in complex with Fab fragment

spinqualitylabelsall models 4xh2, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4xh2 is a 18 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: ACE, ACT, GOL, LDA, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PAXI_HUMAN Cytoskeletal protein involved in actin-membrane attachment at sites of cell adhesion to the extracellular matrix (focal adhesion). Publication Abstract from PubMed Focal adhesion protein paxillin links integrin and growth factor signaling to actin cytoskeleton. Most of paxillin signaling activity is regulated via leucine-rich LD motifs (LD1-LD5) located at the N-terminus. Here, we demonstrate a method to engineer highly selective synthetic antibodies (sABs) against LD2 and LD4 which are binding sites for focal adhesion kinase (FAK) and other proteins. Phage display selections against peptides were used to generate sABs recognizing each LD motif. In the obtained X-ray crystal structures of the LD-sAB complexes the LD motifs are helical and bind sABs through a hydrophobic side, similarly as in the structures with natural paxillin partners. The sABs are capable of pulling down endogenous paxillin in complex with FAK and can visualize paxillin in focal adhesions in cells. They were also used as selective inhibitors to effectively compete with focal adhesion targeting domain of FAK for the binding to LD2 and LD4. The sABs are tools for investigation of paxillin LD binding "platforms" and are capable of inhibiting paxillin interactions; and thereby useful as potential therapeutics in the future. Engineering synthetic antibody inhibitors specific for LD2 or LD4 motifs of paxillin.,Nocula-Lugowska M, Lugowski M, Salgia R, Kossiakoff AA J Mol Biol. 2015 Jun 15. pii: S0022-2836(15)00344-7. doi:, 10.1016/j.jmb.2015.06.004. PMID:26087144 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Paxillin

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