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3.A.5.8.1
The general secretory pathway (Sec-SRP) complex. The Yet1 and Yet3 proteins interact directly with the Sec translocon (Wilson & Barlowe et al., 2010). The Sss1/Sec61γ protein (80aas) has two domains. The cytosolic domain is required for Sec61p interaction while the transmembrane clamp domain is required to complete activation of the translocon after precursor targeting to Sec61p (Wilkinson et al., 2010). However, the apolar surfrace area determines the efficiency of translocon-mediated membrane-protein integration into the endoplasmic reticulum (Öjemalm et al., 2011). The essential Sec62, Sec63 and non-essential Sec66 and Sec72 proteins may comprise an SRP-independent tetrameric translocon enlisting the lumenal chaperone, BiP/Kar2 to ""ratchet"" its substrates into the ER (Feldheim and Schekman 1994; Ast et al. 2013). Cytosolic segments of the Sec61 complex important for promoting the structural transition between the closed and open conformations of the complex have been identified (Mandon et al. 2018). Positively charged residues in multiple cytosolic segments, as well as bulky hydrophobic residues in the L6/7-TMS7 junction may be required for cotranslational translocation or integration of membrane proteins by the Sec61 complex (Mandon et al. 2018). The structure of the yeast post-translational Sec complex (Sec61-Sec63-Sec71-Sec72) by cryo-EM shows that Sec63 tightly associates with Sec61 through interactions in cytosolic, transmembrane, and ER-luminal domains, prying open Sec61's lateral gate and translocation pore, and thus activating the channel for substrate engagement.  Sec63 optimally positions binding sites for cytosolic and luminal chaperones in the complex to enable efficient polypeptide translocation (Itskanov and Park 2019). Further, post-translational translocation is mediated by the association of the Sec61 channel with the membrane protein complex, the Sec62-Sec63 complex, and substrates move through the channel by the luminal BiP ATPase. Wu et al. 2019 determined the cryoEM structure of the S. cerevisiae Sec complex, consisting of the Sec61 channel and the Sec62, Sec63, Sec71 and Sec72 proteins. Sec63 causes wide opening of the lateral gate of the Sec61 channel, priming it for the passage of low-hydrophobicity signal sequences into the lipid phase, without displacing the channel's plug domain. Lateral channel opening is triggered by Sec63 interacting both with cytosolic loops in the C-terminal half of Sec61 and transmembrane segments in the N-terminal half of the Sec61 channel. The cytosolic Brl domain of Sec63 blocks ribosome binding to the channel and recruits Sec71 and Sec72, positioning them for the capture of polypeptides associated with cytosolic Hsp70. The structure thus shows how the Sec61 channel is activated for post-translational protein translocation (Wu et al. 2019).

Accession Number:P33754
Protein Name:Sec66 aka HSS1 aka SEC71 aka YBR171W aka YBR1232
Length:206
Molecular Weight:24231.00
Species:Saccharomyces cerevisiae (Baker's yeast) [4932]
Number of TMSs:1
Location1 / Topology2 / Orientation3: Endoplasmic reticulum membrane1 / Single-pass type II membrane protein2
Substrate protein

Cross database links:

DIP: DIP-1694N
RefSeq: NP_009730.1   
Entrez Gene ID: 852469   
Pfam: PF09802   
KEGG: sce:YBR171W   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0031207 C:Sec62/Sec63 complex
GO:0005515 F:protein binding
GO:0008565 F:protein transporter activity
GO:0030447 P:filamentous growth
GO:0031204 P:posttranslational protein targeting to memb...

References (9)

[1] “Structural and functional characterization of Sec66p, a new subunit of the polypeptide translocation apparatus in the yeast endoplasmic reticulum.”  Feldheim D.et.al.   8257795
[2] “Suppression of a sec63 mutation identifies a novel component of the yeast endoplasmic reticulum translocation apparatus.”  Kurihara T.et.al.   8257794
[3] “Sequence and function analysis of a 4.3 kb fragment of Saccharomyces cerevisiae chromosome II including three open reading frames.”  Schaaff-Gerstenschlaeger I.et.al.   8212898
[4] “Complete DNA sequence of yeast chromosome II.”  Feldmann H.et.al.   7813418
[5] “Approaching a complete repository of sequence-verified protein-encoding clones for Saccharomyces cerevisiae.”  Hu Y.et.al.   17322287
[6] “Assembly of yeast Sec proteins involved in translocation into the endoplasmic reticulum into a membrane-bound multisubunit complex.”  Deshaies R.J.et.al.   2000150
[7] “A Sec63p-BiP complex from yeast is required for protein translocation in a reconstituted proteoliposome.”  Brodsky J.L.et.al.   8253836
[8] “Posttranslational protein transport in yeast reconstituted with a purified complex of Sec proteins and Kar2p.”  Panzner S.et.al.   7758110
[9] “Global analysis of protein expression in yeast.”  Ghaemmaghami S.et.al.   14562106
Structure:
6N3Q   6ND1     

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FASTA formatted sequence
1:	MSEFNETKFS NNGTFFETEE PIVETKSISV YTPLIYVFIL VVSLVMFASS YRKKQAKKIS 
61:	EQPSIFDEND AHDLYFQIKE MSENEKIHEK VLKAALLNRG AESVRRSLKL KELAPQINLL 
121:	YKNGSIGEDY WKRFETEVKL IELEFKDTLQ EAERLQPGWV QLFVMVCKEI CFNQALSRRY 
181:	QSILKRKEVC IKEWELKINN DGRLVN