期刊
MOLECULAR CELL
卷 81, 期 19, 页码 3934-+出版社
CELL PRESS
DOI: 10.1016/j.molcel.2021.07.031
关键词
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资金
- ERC [724425]
- Dutch Research Council (NWO) [741.018.201]
- ERC advanced grant COMP-MICR-CROW-MEM
- European Union Horizon 2020 program INFRAIA project Epic-XS [823839]
- Netherlands Electron Microscopy Infrastructure
- European Research Council (ERC) [724425] Funding Source: European Research Council (ERC)
Human SPC has two functional paralogs with distinct proteolytic subunits, and its structure plays a key role in the specificity for SPs based on the length of their hydrophobic segments.
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.
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