PDBsum entry: 2kb8

Hormone

PDB id: 2kb8

Contents

Protein chain

37 a.a. *

* Residue conservation analysis

PDB id:

2kb8

Name:

Hormone

Title:

The dynamic alpha-helix structure of micelle-bound human amylin.

Structure:

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

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: iapp. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: recombinant 15n-labeled amylin was purchased from rpeptide

NMR struc:

30 models

Authors:

S.M.Patil,S.Xu,S.R.Sheftic,A.T.Alexandrescu

Key ref:

S.M.Patil et al. (2009). Dynamic alpha-helix structure of micelle-bound human amylin. J Biol Chem, 284, 11982-11991. PubMed id: 19244249 DOI: 10.1074/jbc.M809085200

Date:

21-Nov-08 Release date: 24-Feb-09

Protein chain

P10997  (IAPP_HUMAN) -  Islet amyloid polypeptide

Seq: 89 a.a.

Struc: 37 a.a.

 Gene Ontology (GO) functional annotation 

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

DOI no: 10.1074/jbc.M809085200

J Biol Chem 284:11982-11991 (2009)

PubMed id: 19244249

Dynamic alpha-helix structure of micelle-bound human amylin.

S.M.Patil, S.Xu, S.R.Sheftic, A.T.Alexandrescu.

ABSTRACT

Amylin is an endocrine hormone that regulates metabolism. In patients afflicted with type 2 diabetes, amylin is found in fibrillar deposits in the pancreas. Membranes are thought to facilitate the aggregation of amylin, and membrane-bound oligomers may be responsible for the islet beta-cell toxicity that develops during type 2 diabetes. To better understand the structural basis for the interactions between amylin and membranes, we determined the NMR structure of human amylin bound to SDS micelles. The first four residues in the structure are constrained to form a hairpin loop by the single disulfide bond in amylin. The last nine residues near the C terminus are unfolded. The core of the structure is an alpha-helix that runs from about residues 5-28. A distortion or kink near residues 18-22 introduces pliancy in the angle between the N- and C-terminal segments of the alpha-helix. Mobility, as determined by (15)N relaxation experiments, increases from the N to the C terminus and is strongly correlated with the accessibility of the polypeptide to spin probes in the solution phase. The spin probe data suggest that the segment between residues 5 and 17 is positioned within the hydrophobic lipid environment, whereas the amyloidogenic segment between residues 20 and 29 is at the interface between the lipid and solvent. This orientation may direct the aggregation of amylin on membranes, whereas coupling between the two segments may mediate the transition to a toxic structure.

Selected figure(s)

Figure 1.
^1H-^15N HSQC spectrum of micelle-bound amylin annotated with backbone NMR assignments. Side chain correlations are indicated with the superscript SC. Conditions are as follows: 0.5 mm ^15N-amylin, 100 mm SDS, 60 mm acetate, pH 4.6, 37 °C.

Figure 5.
Spin probe studies of amylin positioning in SDS micelles. A, effects of MnCl[2] on ^1H-^15N HSQC cross-peak intensities. B, effects of 16-doxyl-stearate on cross-peak intensities. C, control ^1H-^15N HSQC of micelle-bound amylin showing intensities in the absence of paramagnetic spin probes. D, spectrum in the presence of 1.0 mm MnCl[2]. The correlations that persist are labeled. Correlations from side chains are indicated with the superscript SC.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2009, 284, 11982-11991) copyright 2009.

Figures were selected by an automated process.