PDBsum entry: 3g7v

Sugar binding protein, hormone

PDB-id: 3g7v

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PROCHECK

Protein chains

399 a.a. *

Ligands

MAL ×4

SO4 ×15

GOL ×5

Waters ×862

* Residue conservation analysis

Tools

Clefts Calculation

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PDB id:

3g7v

Name:

Sugar binding protein, hormone

Title:

Islet amyloid polypeptide (iapp or amylin) fused to maltose binding protein

Structure:

Maltose-binding periplasmic protein, islet amyloid polypeptide fusion protein. Chain: a, b, c, d. Synonym: mmbp, maltodextrin-binding protein, amylin, diabetes-associated peptide, dap, insulinoma amyloid peptide. Engineered: yes

Source:

Escherichia coli, homo sapiens. Organism_taxid: 83333,9606. Gene: male, b4034, jw3994, iapp. Expressed in: escherichia coli. Expression_system_taxid: 562.

UniProt:

Chain : ()

Chain : ()

Resolution:

1.86Å

R-factor:

0.178

R-free:

0.205

Authors:

J.J.W.Wiltzius,M.R.Sawaya,D.Eisenberg

Key ref:

J.J.Wiltzius et al. (2009). Atomic structures of IAPP (amylin) fusions suggest a mechanism for fibrillation and the role of insulin in the process.. Protein Sci, 18, 1521-1530. [PubMed id: 19475663] [DOI: 10.1002/pro.145]

Date:

10-Feb-09

Release date:

23-Jun-09

Related entries:

3g7w

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Surface

Key reference

DOI no: 10.1002/pro.145

Protein Sci 18:1521-1530 (2009)

PubMed id: 19475663

Atomic structures of IAPP (amylin) fusions suggest a mechanism for fibrillation and the role of insulin in the process.

J.J.Wiltzius, S.A.Sievers, M.R.Sawaya, D.Eisenberg.

ABSTRACT

Islet Amyloid Polypeptide (IAPP or amylin) is a peptide hormone produced and stored in the beta-islet cells of the pancreas along with insulin. IAPP readily forms amyloid fibrils in vitro, and the deposition of fibrillar IAPP has been correlated with the pathology of type II diabetes. The mechanism of the conversion that IAPP undergoes from soluble to fibrillar forms has been unclear. By chaperoning IAPP through fusion to maltose binding protein, we find that IAPP can adopt a alpha-helical structure at residues 8-18 and 22-27 and that molecules of IAPP dimerize. Mutational analysis suggests that this dimerization is on the pathway to fibrillation. The structure suggests how IAPP may heterodimerize with insulin, which we confirmed by protein crosslinking. Taken together, these experiments suggest the helical dimerization of IAPP accelerates fibril formation and that insulin impedes fibrillation by blocking the IAPP dimerization interface.