How does Sec63 affect the conformation of Sec61 in yeast?
PLoS Comput Biol
; 17(3): e1008855, 2021 03.
Article
in En
| MEDLINE
| ID: mdl-33780447
ABSTRACT
The Sec complex catalyzes the translocation of proteins of the secretory pathway into the endoplasmic reticulum and the integration of membrane proteins into the endoplasmic reticulum membrane. Some substrate peptides require the presence and involvement of accessory proteins such as Sec63. Recently, a structure of the Sec complex from Saccharomyces cerevisiae, consisting of the Sec61 channel and the Sec62, Sec63, Sec71 and Sec72 proteins was determined by cryo-electron microscopy (cryo-EM). Here, we show by co-precipitation that the Sec61 channel subunit Sbh1 is not required for formation of stable Sec63-Sec61 contacts. Molecular dynamics simulations started from the cryo-EM conformation of Sec61 bound to Sec63 and of unbound Sec61 revealed how Sec63 affects the conformation of Sec61 lateral gate, plug, pore region and pore ring diameter via three intermolecular contact regions. Molecular docking of SRP-dependent vs. SRP-independent signal peptide chains into the Sec61 channel showed that the pore regions affected by presence/absence of Sec63 play a crucial role in positioning the signal anchors of SRP-dependent substrates nearby the lateral gate.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Membrane Transport Proteins
/
Saccharomyces cerevisiae Proteins
/
SEC Translocation Channels
/
Heat-Shock Proteins
Language:
En
Journal:
PLoS Comput Biol
Journal subject:
BIOLOGIA
/
INFORMATICA MEDICA
Year:
2021
Type:
Article
Affiliation country:
Germany