Abstract
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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
Amino Acid Sequence
-
Amyloid / chemistry*
-
Amyloid / genetics
-
Amyloid / isolation & purification
-
Amyloid / metabolism
-
Amyloid / ultrastructure
-
Carrier Proteins / chemistry
-
Carrier Proteins / metabolism
-
Computer Simulation
-
Crystallization
-
Diabetes Mellitus, Type 2 / metabolism
-
Diabetes Mellitus, Type 2 / physiopathology
-
Disulfides / chemistry
-
Histidine / metabolism
-
Humans
-
Hydrogen Bonding
-
Islet Amyloid Polypeptide
-
Islets of Langerhans / chemistry*
-
Maltose-Binding Proteins
-
Models, Molecular
-
Molecular Sequence Data
-
Mutation
-
Protein Conformation
-
Protein Structure, Secondary
-
Protein Structure, Tertiary
-
Recombinant Fusion Proteins / chemistry
-
Recombinant Fusion Proteins / metabolism
-
Sequence Homology, Amino Acid
-
Solubility
-
X-Ray Diffraction
Substances
-
Amyloid
-
Carrier Proteins
-
Disulfides
-
Islet Amyloid Polypeptide
-
Maltose-Binding Proteins
-
Recombinant Fusion Proteins
-
Histidine