Dynamic α-Helix Structure of Micelle-bound Human Amylin

摘要: Amylin is an endocrine hormone that regulates metabolism. In patients afflicted with type 2 diabetes, amylin found in fibrillar deposits the pancreas. Membranes are thought to facilitate aggregation of amylin, and membrane-bound oligomers may be responsible for islet β-cell toxicity develops during diabetes. To better understand structural basis interactions between membranes, we determined NMR structure human bound SDS micelles. The first four residues constrained form a hairpin loop by single disulfide bond amylin. last nine near C terminus unfolded. core α-helix runs from about 5–28. A distortion or kink 18–22 introduces pliancy angle N- C-terminal segments α-helix. Mobility, as 15N relaxation experiments, increases N strongly correlated accessibility polypeptide spin probes solution phase. probe data suggest segment 5 17 positioned within hydrophobic lipid environment, whereas amyloidogenic 20 29 at interface solvent. This orientation direct on coupling two mediate transition toxic structure.