Number of the records: 1
Human insulin analogues modified at the B26 site reveal a hormone conformation that is undetected in the receptor complex
- 1.
SYSNO ASEP 0435229 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Human insulin analogues modified at the B26 site reveal a hormone conformation that is undetected in the receptor complex Author(s) Žáková, Lenka (UOCHB-X) RID, ORCID
Kletvíková, Emília (UOCHB-X)
Lepšík, Martin (UOCHB-X) RID, ORCID
Collinsová, Michaela (UOCHB-X) RID
Watson, C. J. (GB)
Turkenburg, J. P. (GB)
Jiráček, Jiří (UOCHB-X) RID, ORCID
Brzozowski, A. M. (GB)Number of authors 8 Source Title Acta Crystallographica Section D-Biological Crystallography. - : WILEY-BLACKWELL - ISSN 0907-4449
Roč. 70, č. 10 (2014), s. 2765-2774Number of pages 10 s. Language eng - English Country US - United States Keywords insulin ; insulin receptor ; complex ; active form ; analog ; structure Subject RIV CE - Biochemistry R&D Projects GPP207/11/P430 GA ČR - Czech Science Foundation (CSF) GBP208/12/G016 GA ČR - Czech Science Foundation (CSF) Institutional support UOCHB-X - RVO:61388963 UT WOS 000343060900025 EID SCOPUS 84907842181 DOI 10.1107/S1399004714017775 Annotation 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. Workplace Institute of Organic Chemistry and Biochemistry Contact asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Viktorie Chládková, Tel.: 232 002 434 Year of Publishing 2015
Number of the records: 1