2KB8
The dynamic alpha-helix structure of micelle-bound human amylin.
Summary for 2KB8
| Entry DOI | 10.2210/pdb2kb8/pdb |
| Descriptor | Islet amyloid polypeptide (1 entity in total) |
| Functional Keywords | iapp, amyloid, micelle-bound, type ii diabetes, hormone, amidation, cleavage on pair of basic residues, polymorphism, secreted |
| Biological source | Homo sapiens (Human) |
| Cellular location | Secreted: P10997 |
| Total number of polymer chains | 1 |
| Total formula weight | 3909.30 |
| Authors | Patil, S.M.,Xu, S.,Sheftic, S.R.,Alexandrescu, A.T. (deposition date: 2008-11-21, release date: 2009-02-24, Last modification date: 2024-11-27) |
| Primary citation | Patil, S.M.,Xu, S.,Sheftic, S.R.,Alexandrescu, A.T. Dynamic alpha-helix structure of micelle-bound human amylin. J.Biol.Chem., 284:11982-11991, 2009 Cited by PubMed Abstract: Amylin is an endocrine hormone that regulates metabolism. In patients afflicted with type 2 diabetes, amylin is found in fibrillar deposits in the pancreas. Membranes are thought to facilitate the aggregation of amylin, and membrane-bound oligomers may be responsible for the islet beta-cell toxicity that develops during type 2 diabetes. To better understand the structural basis for the interactions between amylin and membranes, we determined the NMR structure of human amylin bound to SDS micelles. The first four residues in the structure are constrained to form a hairpin loop by the single disulfide bond in amylin. The last nine residues near the C terminus are unfolded. The core of the structure is an alpha-helix that runs from about residues 5-28. A distortion or kink near residues 18-22 introduces pliancy in the angle between the N- and C-terminal segments of the alpha-helix. Mobility, as determined by (15)N relaxation experiments, increases from the N to the C terminus and is strongly correlated with the accessibility of the polypeptide to spin probes in the solution phase. The spin probe data suggest that the segment between residues 5 and 17 is positioned within the hydrophobic lipid environment, whereas the amyloidogenic segment between residues 20 and 29 is at the interface between the lipid and solvent. This orientation may direct the aggregation of amylin on membranes, whereas coupling between the two segments may mediate the transition to a toxic structure. PubMed: 19244249DOI: 10.1074/jbc.M809085200 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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