4UNH

Human insulin B26Gly mutant crystal structure

4UNH の概要

• エントリーDOI: 10.2210/pdb4unh/pdb
• 関連するPDBエントリー: 4UNE 4UNG
• 分子名称: INSULIN A CHAIN, INSULIN B CHAIN, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: hormone, b26 site
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Secreted: P01308 P01308
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 5807.59

構造登録者

Zakova, L.,Klevtikova, E.,Lepsik, M.,Collinsova, M.,Watson, C.J.,Turkenburg, J.P.,Jiracek, J.,Brzozowski, A.M. (登録日: 2014-05-28, 公開日: 2014-10-15, 最終更新日: 2024-11-20)

主引用文献

Zakova, L.,Klevtikova, E.,Lepsik, M.,Collinsova, M.,Watson, C.J.,Turkenburg, J.P.,Jiracek, J.,Brzozowski, A.M.
Human Insulin Analogues Modified at the B26 Site Reveal a Hormone Conformation that is Undetected in the Receptor Complex
Acta Crystallogr.,Sect.D, 70:2765-, 2014

PubMed Abstract: The structural characterization of the insulin-insulin receptor (IR) interaction still lacks the conformation of the crucial B21-B30 insulin region, which must be different from that in its storage forms to ensure effective receptor binding. Here, it is shown that insulin analogues modified by natural amino acids at the TyrB26 site can represent an active form of this hormone. In particular, [AsnB26]-insulin and [GlyB26]-insulin attain a B26-turn-like conformation that differs from that in all known structures of the native hormone. It also matches the receptor interface, avoiding substantial steric clashes. This indicates that insulin may attain a B26-turn-like conformation upon IR binding. Moreover, there is an unexpected, but significant, binding specificity of the AsnB26 mutant for predominantly the metabolic B isoform of the receptor. As it is correlated with the B26 bend of the B-chain of the hormone, the structures of AsnB26 analogues may provide the first structural insight into the structural origins of differential insulin signalling through insulin receptor A and B isoforms.

PubMed: 25286859
DOI: 10.1107/S1399004714017775

実験手法

X-RAY DIFFRACTION (2.75 Å)