2KQP

NMR Structure of Proinsulin

2KQP の概要

• エントリーDOI: 10.2210/pdb2kqp/pdb
• NMR情報: BMRB: 16608
• 分子名称: Insulin (1 entity in total)
• 機能のキーワード: proinsulin, carbohydrate metabolism, cleavage on pair of basic residues, diabetes mellitus, disease mutation, disulfide bond, glucose metabolism, hormone, pharmaceutical, secreted
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P01308
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 9379.58

構造登録者

Yang, Y.,Hua, Q.X.,Mackin, R.B.,Weiss, M.A. (登録日: 2009-11-12, 公開日: 2010-01-26, 最終更新日: 2024-10-30)

主引用文献

Yang, Y.,Hua, Q.X.,Liu, J.,Shimizu, E.H.,Choquette, M.H.,Mackin, R.B.,Weiss, M.A.
Solution structure of proinsulin: connecting domain flexibility and prohormone processing.
J.Biol.Chem., 285:7847-7851, 2010

PubMed Abstract: The folding of proinsulin, the single-chain precursor of insulin, ensures native disulfide pairing in pancreatic beta-cells. Mutations that impair folding cause neonatal diabetes mellitus. Although the classical structure of insulin is well established, proinsulin is refractory to crystallization. Here, we employ heteronuclear NMR spectroscopy to characterize a monomeric analogue. Proinsulin contains a native-like insulin moiety (A- and B-domains); the tethered connecting (C) domain (as probed by {(1)H}-(15)N nuclear Overhauser enhancements) is progressively less ordered. Although the BC junction is flexible, residues near the CA junction exhibit alpha-helical-like features. Relative to canonical alpha-helices, however, segmental (13)C(alpha/beta) chemical shifts are attenuated, suggesting that this junction and contiguous A-chain residues are molten. We propose that flexibility at each C-domain junction facilitates prohormone processing. Studies of protease SPC3 (PC1/3) suggest that C-domain sequences contribute to cleavage site selection. The structure of proinsulin provides a foundation for studies of insulin biosynthesis and its impairment in monogenic forms of diabetes mellitus.

PubMed: 20106974
DOI: 10.1074/jbc.C109.084921

実験手法

SOLUTION NMR