7p2p
Human Signal Peptidase Complex Paralog A (SPC-A)
Structural highlights
FunctionSC11A_HUMAN Catalytic component of the signal peptidase complex (SPC) which catalyzes the cleavage of N-terminal signal sequences from nascent proteins as they are translocated into the lumen of the endoplasmic reticulum (PubMed:34388369). Specifically cleaves N-terminal signal peptides that contain a hydrophobic alpha-helix (h-region) shorter than 18-20 amino acids (PubMed:34388369).[1] Publication Abstract from PubMedThe signal peptidase complex (SPC) is an essential membrane complex in the endoplasmic reticulum (ER), where it removes signal peptides (SPs) from a large variety of secretory pre-proteins with exquisite specificity. Although the determinants of this process have been established empirically, the molecular details of SP recognition and removal remain elusive. Here, we show that the human SPC exists in two functional paralogs with distinct proteolytic subunits. We determined the atomic structures of both paralogs using electron cryo-microscopy and structural proteomics. The active site is formed by a catalytic triad and abuts the ER membrane, where a transmembrane window collectively formed by all subunits locally thins the bilayer. Molecular dynamics simulations indicate that this unique architecture generates specificity for SPs based on the length of their hydrophobic segments. Structure of the human signal peptidase complex reveals the determinants for signal peptide cleavage.,Liaci AM, Steigenberger B, Telles de Souza PC, Tamara S, Grollers-Mulderij M, Ogrissek P, Marrink SJ, Scheltema RA, Forster F Mol Cell. 2021 Oct 7;81(19):3934-3948.e11. doi: 10.1016/j.molcel.2021.07.031. , Epub 2021 Aug 12. PMID:34388369[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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