Atomic structure of the cross-beta spine of islet amyloid polypeptide (amylin).
Human islet amyloid polypeptide (IAPP or amylin) is a 37-residue hormone found as fibrillar deposits in pancreatic extracts of nearly all type II diabetics. Although the cellular toxicity of IAPP has been established, the structure of the fibrillar form found in these deposits is unknown. Here we have crystallized two segments from IAPP, which themselves form amyloid-like fibrils. The atomic structures of these two segments, NNFGAIL and SSTNVG, were determined, and form the basis of a model for the most commonly observed, full-length IAPP polymorph.
Howard Hughes Medical Institute, UCLA-DOE Institute for Genomics and Proteomics, Los Angeles, California 90095-1570, USA.
Jed J W
JJ
Wiltzius
Stuart A
SA
Sievers
Michael R
MR
Sawaya
Duilio
D
Cascio
Dmitriy
D
Popov
Christian
C
Riekel
David
D
Eisenberg
D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000648:ultrastructure; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D003198:Computer Simulation; D003460:Crystallization; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology; D004220:Disulfides / Q000737:chemistry; D006639:Histidine / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000737:chemistry*; D058619:Maltose-Binding Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012995:Solubility; D014961:X-Ray Diffraction
D000682:Amyloid; D002352:Carrier Proteins; D004220:Disulfides; D058228:Islet Amyloid Polypeptide; D058619:Maltose-Binding Proteins; D011993:Recombinant Fusion Proteins; D006639:Histidine