5j6z

Structure of anastellin bound to beta-strands A and B from the third type III domain of fibronectin

spinqualitylabelsall models 5j6z Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5j6z is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease FINC_HUMAN Defects in FN1 are the cause of glomerulopathy with fibronectin deposits type 2 (GFND2) [MIM:601894; also known as familial glomerular nephritis with fibronectin deposits or fibronectin glomerulopathy. GFND is a genetically heterogeneous autosomal dominant disorder characterized clinically by proteinuria, microscopic hematuria, and hypertension that leads to end-stage renal failure in the second to fifth decade of life. Function FINC_HUMAN Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin. Fibronectins are involved in cell adhesion, cell motility, opsonization, wound healing, and maintenance of cell shape. Anastellin binds fibronectin and induces fibril formation. This fibronectin polymer, named superfibronectin, exhibits enhanced adhesive properties. Both anastellin and superfibronectin inhibit tumor growth, angiogenesis and metastasis. Anastellin activates p38 MAPK and inhibits lysophospholipid signaling. Publication Abstract from PubMed Anastellin is a small recombinant fragment derived from the extracellular matrix protein fibronectin; it comprises the first type III (FN3) domain without the two N-terminal beta-strands. It inhibits angiogenesis, tumor growth, and metastasis in mouse models and requires endogenous fibronectin for its in vivo anti-angiogenic activity. It binds to fibronectin in vitro and converts the soluble protein to insoluble fibrils that structurally and functionally resemble fibronectin fibrils deposited in the extracellular matrix by cells. Anastellin binds to several FN3 domains in fibronectin, but how it interacts with these domains and why the interactions lead to aggregation of fibronectin are not well understood. In this work, we investigated the interaction between anastellin and the third FN3 domain (3FN3) from fibronectin. We show that anastellin binds with high affinity to a peptide comprising the two N-terminal beta-strands from 3FN3, and we present here the structure of the resulting complex. The peptide and anastellin form a composite FN3 domain, with the two N-terminal beta-strands from 3FN3 bound in place of the two beta-strands that are missing in anastellin. We also demonstrate using disulfide cross-linking that a similar interaction involving the two N-terminal beta-strands of 3FN3 occurs when intact 3FN3 binds to anastellin. 3FN3 adopts a compact globular fold in solution, and to interact with anastellin in a manner consistent with our data, it has to open up and expose a beta-strand edge that is not accessible in the context of the folded domain. The Interaction between the Third Type III Domain from Fibronectin and Anastellin Involves beta-Strand Exchange.,Stine JM, Ahl GJH, Schlenker C, Rusnac DV, Briknarova K Biochemistry. 2017 Sep 5;56(35):4667-4675. doi: 10.1021/acs.biochem.7b00633. Epub, 2017 Aug 18. PMID:28820240 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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