PDBsum entry 5k5g

Hormone

PDB id: 5k5g

Contents

Protein chains

21 a.a.

44 a.a.

PDB id:

5k5g

Name:

Hormone

Title:

Structure of human islet amyloid polypeptide in complex with an engineered binding protein

Structure:

Islet amyloid polypeptide. Chain: a. Synonym: amylin,diabetes-associated peptide,dap,insulinoma amyloid peptide. Engineered: yes. Hi18. Chain: b, c. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Organ: pancreas. Cell: b-cell. Gene: iapp. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic construct.

NMR struc:

10 models

Authors:

E.A.Mirecka,S.Feuerstein,L.Gremer,G.F.Schroeder,M.Stoldt,D.Willbold, W.Hoyer

Key ref:

E.A.Mirecka et al. (2016). β-Hairpin of Islet Amyloid Polypeptide Bound to an Aggregation Inhibitor. Sci Rep, 6, 33474. PubMed id: 27641459 DOI: 10.1038/srep33474

Date:

23-May-16 Release date: 26-Oct-16

Protein chain

P10997  (IAPP_HUMAN) -  Islet amyloid polypeptide from Homo sapiens

Seq: 89 a.a.

Struc: 21 a.a.

Protein chains

No UniProt id for this chain

Struc: 44 a.a.

DOI no: 10.1038/srep33474

Sci Rep 6:33474 (2016)

PubMed id: 27641459

β-Hairpin of Islet Amyloid Polypeptide Bound to an Aggregation Inhibitor.

E.A.Mirecka, S.Feuerstein, L.Gremer, G.F.Schröder, M.Stoldt, D.Willbold, W.Hoyer.

ABSTRACT

In type 2 diabetes, the formation of islet amyloid consisting of islet amyloid polypeptide (IAPP) is associated with reduction in β-cell mass and contributes to the failure of islet cell transplantation. Rational design of inhibitors of IAPP amyloid formation has therapeutic potential, but is hampered by the lack of structural information on inhibitor complexes of the conformationally flexible, aggregation-prone IAPP. Here we characterize a β-hairpin conformation of IAPP in complex with the engineered binding protein β-wrapin HI18. The β-strands correspond to two amyloidogenic motifs, 12-LANFLVH-18 and 22-NFGAILS-28, which are connected by a turn established around Ser-20. Besides backbone hydrogen bonding, the IAPP:HI18 interaction surface is dominated by non-polar contacts involving hydrophobic side chains of the IAPP β-strands. Apart from monomers, HI18 binds oligomers and fibrils and inhibits IAPP aggregation and toxicity at low substoichiometric concentrations. The IAPP β-hairpin can serve as a molecular recognition motif enabling control of IAPP aggregation.