title: Signal peptide cleavage of a type I membrane protein, HCMV US11, is dependent on its membrane 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.
authors: Harvard Medical School, Department of Pathology, Boston, MA 02115, USA.
authors: A
authors: A
authors: Rehm
authors: P
authors: P
authors: Stern
authors: H L
authors: HL
authors: Ploegh
authors: D
authors: D
authors: Tortorella
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012995:Solubility; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D008562:Membrane Glycoproteins; D021382:Protein Sorting Signals; D016601:RNA-Binding Proteins; C074546:US11 protein, herpesvirus; D014764:Viral Proteins