Počet záznamů: 1
Human insulin analogues modified at the B26 site reveal a hormone conformation that is undetected in the receptor complex
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SYSNO ASEP 0435229 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Human insulin analogues modified at the B26 site reveal a hormone conformation that is undetected in the receptor complex Tvůrce(i) 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)Celkový počet autorů 8 Zdroj.dok. Acta Crystallographica Section D-Biological Crystallography. - : WILEY-BLACKWELL - ISSN 0907-4449
Roč. 70, č. 10 (2014), s. 2765-2774Poč.str. 10 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova insulin ; insulin receptor ; complex ; active form ; analog ; structure Vědní obor RIV CE - Biochemie CEP GPP207/11/P430 GA ČR - Grantová agentura ČR GBP208/12/G016 GA ČR - Grantová agentura ČR Institucionální podpora UOCHB-X - RVO:61388963 UT WOS 000343060900025 EID SCOPUS 84907842181 DOI 10.1107/S1399004714017775 Anotace 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. Pracoviště Ústav organické chemie a biochemie Kontakt asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Viktorie Chládková, Tel.: 232 002 434 Rok sběru 2015
Počet záznamů: 1