5k5g

Structure of human islet amyloid polypeptide in complex with an engineered binding protein

spinqualitylabelsall models 5k5g Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5k5g is a 3 chain structure with sequence from Homo sapiens and Synthetic construct. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR, 10 models Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function IAPP_HUMAN Selectively inhibits insulin-stimulated glucose utilization and glycogen deposition in muscle, while not affecting adipocyte glucose metabolism. Publication Abstract from PubMed In type 2 diabetes, the formation of islet amyloid consisting of islet amyloid polypeptide (IAPP) is associated with reduction in beta-cell mass and contributes to the failure of islet cell transplantation. Rational design of inhibitors of IAPP amyloid formation has therapeutic potential, but is hampered by the lack of structural information on inhibitor complexes of the conformationally flexible, aggregation-prone IAPP. Here we characterize a beta-hairpin conformation of IAPP in complex with the engineered binding protein beta-wrapin HI18. The beta-strands correspond to two amyloidogenic motifs, 12-LANFLVH-18 and 22-NFGAILS-28, which are connected by a turn established around Ser-20. Besides backbone hydrogen bonding, the IAPP:HI18 interaction surface is dominated by non-polar contacts involving hydrophobic side chains of the IAPP beta-strands. Apart from monomers, HI18 binds oligomers and fibrils and inhibits IAPP aggregation and toxicity at low substoichiometric concentrations. The IAPP beta-hairpin can serve as a molecular recognition motif enabling control of IAPP aggregation. beta-Hairpin of Islet Amyloid Polypeptide Bound to an Aggregation Inhibitor.,Mirecka EA, Feuerstein S, Gremer L, Schroder GF, Stoldt M, Willbold D, Hoyer W Sci Rep. 2016 Sep 19;6:33474. doi: 10.1038/srep33474. PMID:27641459 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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