3G7W

Islet Amyloid Polypeptide (IAPP or Amylin) Residues 1 to 22 fused to Maltose Binding Protein

Summary for 3G7W

• Entry DOI: 10.2210/pdb3g7w/pdb
• Related: 3G7V
• Related PRD ID: PRD_900009
• Descriptor: Maltose-binding periplasmic protein, Islet amyloid polypeptide fusion protein, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, SULFATE ION, ... (5 entities in total)
• Functional Keywords: native fold for amyloidogenic protein, sugar transport, transport, amidation, amyloid, cleavage on pair of basic residues, hormone, secreted, sugar binding protein
• Biological source: Escherichia coli; More
• Total number of polymer chains: 1
• Total formula weight: 45539.45

Authors

Wiltzius, J.J.W.,Sawaya, M.R.,Eisenberg, D. (deposition date: 2009-02-11, release date: 2009-06-23, Last modification date: 2024-11-27)

Primary citation

Wiltzius, J.J.,Sievers, S.A.,Sawaya, M.R.,Eisenberg, D.
Atomic structures of IAPP (amylin) fusions suggest a mechanism for fibrillation and the role of insulin in the process
Protein Sci., 18:1521-1530, 2009

PubMed 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.

PubMed: 19475663
DOI: 10.1002/pro.145

Experimental method

X-RAY DIFFRACTION (1.75 Å)