2L86

Solution NMR structure of human amylin in SDS micelles at pH 7.3

2L86 の概要

• エントリーDOI: 10.2210/pdb2l86/pdb
• NMR情報: BMRB: 17394
• 分子名称: Islet amyloid polypeptide (1 entity in total)
• 機能のキーワード: iapp, apoptosis
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P10997
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 3907.31

構造登録者

Nanga, R.,Brender, J.R.,Vivekanandan, S.,Ramamoorthy, A. (登録日: 2011-01-04, 公開日: 2011-07-13, 最終更新日: 2024-11-27)

主引用文献

Nanga, R.P.,Brender, J.R.,Vivekanandan, S.,Ramamoorthy, A.
Structure and membrane orientation of IAPP in its natively amidated form at physiological pH in a membrane environment.
Biochim.Biophys.Acta, 1808:2337-2342, 2011

PubMed Abstract: Human islet amyloid polypeptide is a hormone coexpressed with insulin by pancreatic beta-cells. For reasons not clearly understood, hIAPP aggregates in type II diabetics to form oligomers that interfere with beta-cell function, eventually leading to the loss of insulin production. The cellular membrane catalyzes the formation of amyloid deposits and is a target of amyloid toxicity through disruption of the membrane's structural integrity. Therefore, there is considerable current interest in solving the 3D structure of this peptide in a membrane environment. NMR experiments could not be directly utilized in lipid bilayers due to the rapid aggregation of the peptide. To overcome this difficulty, we have solved the structure of the naturally occurring peptide in detergent micelles at a neutral pH. The structure has an overall kinked helix motif, with residues 7-17 and 21-28 in a helical conformation, and with a 3(10) helix from Gly 33-Asn 35. In addition, the angle between the N- and C-terminal helices is constrained to 85°. The greater helical content of human IAPP in the amidated versus free acid form is likely to play a role in its aggregation and membrane disruptive activity.

PubMed: 21723249
DOI: 10.1016/j.bbamem.2011.06.012

実験手法

SOLUTION NMR