7P2P

Human Signal Peptidase Complex Paralog A (SPC-A)

Summary for 7P2P

• Entry DOI: 10.2210/pdb7p2p/pdb
• Related: 7P2Q
• EMDB information: 13171 13172
• Descriptor: Signal peptidase complex catalytic subunit SEC11A, Signal peptidase complex subunit 3, Signal peptidase complex subunit 2, ... (5 entities in total)
• Functional Keywords: endoplasmic reticulum, signal peptide, serine protease, membrane complex, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 93339.05

Authors

Liaci, A.M.,Foerster, F. (deposition date: 2021-07-06, release date: 2021-10-06, Last modification date: 2024-11-13)

Primary citation

Liaci, A.M.,Steigenberger, B.,Telles de Souza, P.C.,Tamara, S.,Grollers-Mulderij, M.,Ogrissek, P.,Marrink, S.J.,Scheltema, R.A.,Forster, F.
Structure of the human signal peptidase complex reveals the determinants for signal peptide cleavage.
Mol.Cell, 81:3934-3948.e11, 2021

PubMed Abstract: The 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.

PubMed: 34388369
DOI: 10.1016/j.molcel.2021.07.031

Experimental method

ELECTRON MICROSCOPY (4.9 Å)