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Signal peptide cleavage of a type I membrane protein, HCMV US11, is dependent on its membrane anchor

Official URL:https://doi.org/10.1093/emboj/20.7.1573
PubMed:View item in PubMed
Creators Name:Rehm, A. and Stern, P. and Ploegh, H.L. and Tortorella, D.
Journal Title:EMBO Journal
Journal Abbreviation:EMBO J
Page Range:1573-1582
Date:2 April 2001
Keywords:ER Subdomains, HCMV US11, Posttranslational ER Processing, Signal Sequence Cleavage, Transmembrane Anchor
Abstract:The human cytomegalovirus (HCMV) US11 polypeptide is a type I membrane glycoprotein that targets major histocompatibility complex (MHC) class I molecules for destruction in a proteasome-dependent manner. Although the US11 signal sequence appears to be a classical N-terminal signal peptide in terms of its sequence and cleavage site, a fraction of newly synthesized US11 molecules retain the signal peptide after the N-linked glycan has been attached and translation of the US11 polypeptide has been completed. Delayed cleavage of the US11 signal peptide is determined by the first four residues, the so-called n-region of the signal peptide. Its replacement with the four N-terminal residues of the H-2K b signal sequence eliminates delayed cleavage. Surprisingly, a second region that affects the rate and extent of signal peptide cleavage is the transmembrane region close to the C-terminus of US11. Deletion of the transmembrane region of US11 (US11-180) significantly delays processing, a delay overcome by replacement with the H-2K b signal sequence. Thus, elements at a considerable distance from the signal sequence affect its cleavage.
Publisher:Nature Publishing Group (U.S.A.)
Item Type:Article

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