@article {48699,
	title = {Structure and topology around the cleavage site regulate post-translational cleavage of the HIV-1 gp160 signal peptide.},
	journal = {eLife},
	volume = {6},
	year = {2017},
	month = {2017 Jul 28},
	abstract = {<p>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 that 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.</p>
},
	issn = {2050-084X},
	doi = {10.7554/eLife.26067},
	author = {Snapp, Erik Lee and McCaul, Nicholas and Quandte, Matthias and Cabartova, Zuzana and Bontjer, Ilja and K{\"a}llgren, Carolina and Nilsson, IngMarie and Land, Aafke and von Heijne, Gunnar and Sanders, Rogier W and Braakman, Ineke}
}
