Human insulin analogues modified at the B26 site reveal a hormone conformation that is undetected in the receptor complex

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F14%3A00435229" target="_blank" >RIV/61388963:_____/14:00435229 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1107/S1399004714017775" target="_blank" >http://dx.doi.org/10.1107/S1399004714017775</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1107/S1399004714017775" target="_blank" >10.1107/S1399004714017775</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Human insulin analogues modified at the B26 site reveal a hormone conformation that is undetected in the receptor complex

Popis výsledku v původním jazyce

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 isshown 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 int

Název v anglickém jazyce

Human insulin analogues modified at the B26 site reveal a hormone conformation that is undetected in the receptor complex

Popis výsledku anglicky

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 isshown 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 int

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CE - Biochemie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2014

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Acta Crystallographica Section D-Biological Crystallography

ISSN

0907-4449

e-ISSN

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Svazek periodika

70

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

2765-2774

Kód UT WoS článku

000343060900025

EID výsledku v databázi Scopus

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