title: Idealized models of protofilaments of human islet amyloid polypeptide.
abstract: Fibrils formed by assembly of human islet amyloid polypeptide (hIAPP) are found in most patients with type II diabetes. Structurally, these fibrils are composed of multiple protofilaments and are characterized by extended beta sheets, variable helical twists, and different morphologies. We have previously derived models for the hIAPP protofilament using simulations constrained by data from EPR spectroscopy. In the current work, these models were used as a basis for generating idealized hIAPP protofilaments with symmetrical geometrical properties using a new algorithm, MFIBRIL. We show good agreement of the idealized protofilaments with experimental data for amino acid side chain orientations and geometrical features including the inter-β sheet distance and the protofilament radius. These idealized protofilaments can be used in MFIBRIL to generate fibril models that may be experimentally testable at the molecular level. MFIBRIL can also be used for building structures of any repetitive molecular assembly starting with a single building block obtained from any source.
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Yiyu
authors.initials: Y
authors.lastname: Li
authors.forename: Ma'mon M
authors.initials: MM
authors.lastname: Hatmal
authors.forename: Ralf
authors.initials: R
authors.lastname: Langen
authors.forename: Ian S
authors.initials: IS
authors.lastname: Haworth
mesh_terms: D000465:Algorithms; D000596:Amino Acids / Q000737:chemistry*; D003198:Computer Simulation; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000737:chemistry*; D008958:Models, Molecular; D017510:Protein Folding; D017433:Protein Structure, Secondary
chemical_list: D000596:Amino Acids; D058228:Islet Amyloid Polypeptide