PDBsum entry: 2kj7

Hormone

PDB id: 2kj7

Contents

Protein chain

38 a.a. *

* Residue conservation analysis

PDB id:

2kj7

Name:

Hormone

Title:

Three-dimensional nmr structure of rat islet amyloid polypeptide in dpc micelles

Structure:

Islet amyloid polypeptide. Chain: a. Fragment: rat iapp, unp residues 38-74. Synonym: amylin, diabetes-associated peptide, dap. Engineered: yes

Source:

Rattus norvegicus. Brown rat,rat,rats. Organism_taxid: 10116. Gene: iapp

NMR struc:

10 models

Authors:

R.Nanga,J.R.Brender,J.Xu,K.Hartman,V.Subramanian, A.Ramamoorthy

Key ref:

R.P.Nanga et al. (2009). Three-dimensional structure and orientation of rat islet amyloid polypeptide protein in a membrane environment by solution NMR spectroscopy. J Am Chem Soc, 131, 8252-8261. PubMed id: 19456151 DOI: 10.1021/ja9010095

Date:

22-May-09 Release date: 23-Jun-09

Protein chain

P12969  (IAPP_RAT) -  Islet amyloid polypeptide

Seq: 93 a.a.

Struc: 38 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 

• Cellular component: extracellular region (1 term)
• Biochemical function: hormone activity (1 term)

DOI no: 10.1021/ja9010095

J Am Chem Soc 131:8252-8261 (2009)

PubMed id: 19456151

Three-dimensional structure and orientation of rat islet amyloid polypeptide protein in a membrane environment by solution NMR spectroscopy.

R.P.Nanga, J.R.Brender, J.Xu, K.Hartman, V.Subramanian, A.Ramamoorthy.

ABSTRACT

Islet amyloid polypeptide (IAPP or amylin) is a 37-residue peptide hormone associated with glucose metabolism that is cosecreted with insulin by beta-cells in the pancreas. Since human IAPP is a highly amyloidogenic peptide, it has been suggested that the formation of IAPP amyloid fibers is responsible for the death of beta-cells during the early stages of type II diabetes. It has been hypothesized that transient membrane-bound alpha-helical structures of human IAPP are precursors to the formation of these amyloid deposits. On the other hand, rat IAPP forms transient alpha-helical structures but does not progress further to form amyloid fibrils. To understand the nature of this intermediate state and the difference in toxicity between the rat and human versions of IAPP, we have solved the high-resolution structure of rat IAPP in the membrane-mimicking detergent micelles composed of dodecylphosphocholine. The structure is characterized by a helical region spanning the residues A5 to S23 and a disordered C-terminus. A distortion in the helix is seen at R18 and S19 that may be involved in receptor binding. Paramagnetic quenching NMR experiments indicate that rat IAPP is bound on the surface of the micelle, in agreement with other nontoxic forms of IAPP. A comparison to the detergent-bound structures of other IAPP variants indicates that the N-terminal region may play a crucial role in the self-association and toxicity of IAPP by controlling access to the putative dimerization interface on the hydrophobic face of the amphipathic helix.