Structure and topology around the cleavage site regulate post-translational cleavage of the HIV-1 gp160 signal peptide

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F75010330%3A_____%2F17%3A00011797" target="_blank" >RIV/75010330:_____/17:00011797 - isvavai.cz</a>

Výsledek na webu

<a href="https://elifesciences.org/articles/26067" target="_blank" >https://elifesciences.org/articles/26067</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.7554/eLife.26067" target="_blank" >10.7554/eLife.26067</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Structure and topology around the cleavage site regulate post-translational cleavage of the HIV-1 gp160 signal peptide

Popis výsledku v původním jazyce

Like all other secretory proteins, the HIV-1 envelope glycoprotein gp160 is targeted to the endoplasmic reticulum (ER) by its signal peptide during synthesis. Proper gp160 folding in the ER requires core glycosylation, disulfide-bond formation and proline isomerization. Signal-peptide cleavage occurs only late after gp160 chain termination and is dependent on folding of the soluble subunit gp120 to a near-native conformation. We here detail the mechanism by which co-translational signal-peptide cleavage is prevented. Conserved residues from the signal peptide and residues downstream of the canonical cleavage site form an extended alpha-helix in the ER membrane, which covers the cleavage site, thus preventing cleavage. A point mutation in the signal peptide breaks the alpha helix allowing co-translational cleavage. We demonstrate that postponed cleavage of gp160 enhances functional folding of the molecule. The change to early cleavage results in decreased viral fitness compared to wild-type HIV.

Název v anglickém jazyce

Structure and topology around the cleavage site regulate post-translational cleavage of the HIV-1 gp160 signal peptide

Popis výsledku anglicky

Like all other secretory proteins, the HIV-1 envelope glycoprotein gp160 is targeted to the endoplasmic reticulum (ER) by its signal peptide during synthesis. Proper gp160 folding in the ER requires core glycosylation, disulfide-bond formation and proline isomerization. Signal-peptide cleavage occurs only late after gp160 chain termination and is dependent on folding of the soluble subunit gp120 to a near-native conformation. We here detail the mechanism by which co-translational signal-peptide cleavage is prevented. Conserved residues from the signal peptide and residues downstream of the canonical cleavage site form an extended alpha-helix in the ER membrane, which covers the cleavage site, thus preventing cleavage. A point mutation in the signal peptide breaks the alpha helix allowing co-translational cleavage. We demonstrate that postponed cleavage of gp160 enhances functional folding of the molecule. The change to early cleavage results in decreased viral fitness compared to wild-type HIV.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30303 - Infectious Diseases

Projekt

—

Návaznosti

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

eLIFE

ISSN

2050-084X

e-ISSN

—

Svazek periodika

6

Číslo periodika v rámci svazku

July

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

25

Strana od-do

nestrankovano

Kód UT WoS článku

000408198100001

EID výsledku v databázi Scopus

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