[English] 日本語
Yorodumi Papers
- Database of articles cited by EMDB/PDB/SASBDB data -

+
Search query

Keywords
Structure methods
Author
Journal
IF

-
Structure paper

TitleA common mechanism of Sec61 translocon inhibition by small molecules.
Journal, issue, pagesNat Chem Biol, Vol. 19, Issue 9, Page 1063-1071, Year 2023
Publish dateMay 11, 2023
AuthorsSamuel Itskanov / Laurie Wang / Tina Junne / Rumi Sherriff / Li Xiao / Nicolas Blanchard / Wei Q Shi / Craig Forsyth / Dominic Hoepfner / Martin Spiess / Eunyong Park /
PubMed AbstractThe Sec61 complex forms a protein-conducting channel in the endoplasmic reticulum membrane that is required for secretion of soluble proteins and production of many membrane proteins. Several natural ...The Sec61 complex forms a protein-conducting channel in the endoplasmic reticulum membrane that is required for secretion of soluble proteins and production of many membrane proteins. Several natural and synthetic small molecules specifically inhibit Sec61, generating cellular effects that are useful for therapeutic purposes, but their inhibitory mechanisms remain unclear. Here we present near-atomic-resolution structures of human Sec61 inhibited by a comprehensive panel of structurally distinct small molecules-cotransin, decatransin, apratoxin, ipomoeassin, mycolactone, cyclotriazadisulfonamide and eeyarestatin. All inhibitors bind to a common lipid-exposed pocket formed by the partially open lateral gate and plug domain of Sec61. Mutations conferring resistance to the inhibitors are clustered at this binding pocket. The structures indicate that Sec61 inhibitors stabilize the plug domain in a closed state, thereby preventing the protein-translocation pore from opening. Our study provides the atomic details of Sec61-inhibitor interactions and the structural framework for further pharmacological studies and drug design.
External linksNat Chem Biol / PubMed:37169959 / PubMed Central
MethodsEM (single particle)
Resolution2.54 - 3.4 Å
Structure data

EMDB-27581, PDB-8dnv:
Cryo-EM structure of the human Sec61 complex in a partially-open apo state (Class 1)
Method: EM (single particle) / Resolution: 3.03 Å

EMDB-27582, PDB-8dnw:
Cryo-EM structure of the human Sec61 complex in a partially-open apo state (Class 2)
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-27583, PDB-8dnx:
Cryo-EM structure of the human Sec61 complex inhibited by cotransin
Method: EM (single particle) / Resolution: 2.98 Å

EMDB-27584, PDB-8dny:
Cryo-EM structure of the human Sec61 complex inhibited by decatransin
Method: EM (single particle) / Resolution: 2.85 Å

EMDB-27585, PDB-8dnz:
Cryo-EM structure of the human Sec61 complex inhibited by apratoxin F
Method: EM (single particle) / Resolution: 2.57 Å

EMDB-27586, PDB-8do0:
Cryo-EM structure of the human Sec61 complex inhibited by mycolactone
Method: EM (single particle) / Resolution: 2.86 Å

EMDB-27587, PDB-8do1:
Cryo-EM structure of the human Sec61 complex inhibited by ipomoeassin F
Method: EM (single particle) / Resolution: 3.01 Å

EMDB-27588, PDB-8do2:
Cryo-EM structure of the human Sec61 complex inhibited by cyclotriazadisulfonamide (CADA)
Method: EM (single particle) / Resolution: 2.95 Å

EMDB-27589, PDB-8do3:
Cryo-EM structure of the human Sec61 complex inhibited by eeyarestatin I
Method: EM (single particle) / Resolution: 3.22 Å

EMDB-29608: Cryo-EM map of chimeric Sec complex (human Sec61 and yeast Sec63-71-72) inhibited by eeyarestatin I
Method: EM (single particle) / Resolution: 2.79 Å

EMDB-29609: Cryo-EM map of chimeric Sec complex (human Sec61 and yeast Sec63-71-72) inhibited by cotransin
Method: EM (single particle) / Resolution: 2.77 Å

EMDB-29610: Cryo-EM map of chimeric Sec complex (human Sec61 and yeast Sec63-71-72) inhibited by apratoxin F
Method: EM (single particle) / Resolution: 2.54 Å

EMDB-29611: Cryo-EM map of chimeric Sec complex (human Sec61 and yeast Sec63-71-72) in a partially-open apo state (Class 1)
Method: EM (single particle) / Resolution: 2.74 Å

EMDB-29612: Cryo-EM map of chimeric Sec complex (human Sec61 and yeast Sec63-71-72) in a partially-open apo state (Class 2)
Method: EM (single particle) / Resolution: 2.84 Å

EMDB-29613: Cryo-EM map of chimeric Sec complex (human Sec61 and yeast Sec63-71-72) inhibited by decatransin
Method: EM (single particle) / Resolution: 2.61 Å

EMDB-29614: Cryo-EM map of chimeric Sec complex (human Sec61 and yeast Sec63-71-72) inhibited by ipomoeassin F (Class 1)
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-29616: Cryo-EM map of chimeric Sec complex (human Sec61 and yeast Sec63-71-72) inhibited by cyclotriazadisulfonamide (CADA)
Method: EM (single particle) / Resolution: 2.85 Å

EMDB-29617: Cryo-EM map of chimeric Sec complex (human Sec61 and yeast Sec63-71-72) inhibited by mycolactone
Method: EM (single particle) / Resolution: 2.94 Å

EMDB-29635: Cryo-EM map of chimeric Sec complex (human Sec61 and yeast Sec63-71-72) inhibited by ipomoeassin F (Class 2)
Method: EM (single particle) / Resolution: 2.7 Å

Chemicals

ChemComp-Q6B:
[(6~{S},7~{S},9~{Z},12~{R})-12-[(~{Z},2~{S},6~{R},7~{R},9~{R})-4,6-dimethyl-7,9-bis(oxidanyl)dec-4-en-2-yl]-7,9-dimethyl-2-oxidanylidene-1-oxacyclododec-9-en-6-yl] (2~{E},4~{E},6~{E},8~{E},10~{E},12~{S},13~{S},15~{S})-4,6,10-trimethyl-12,13,15-tris(oxidanyl)hexadeca-2,4,6,8,10-pentaenoate

ChemComp-HOH:
WATER

ChemComp-SXF:
[(1~{S},3~{R},4~{S},5~{R},6~{R},8~{R},10~{S},23~{R},24~{R},25~{R},26~{R})-5-acetyloxy-6-methyl-4,26-bis(oxidanyl)-17,20-bis(oxidanylidene)-10-pentyl-24-[(~{E})-3-phenylprop-2-enoyl]oxy-2,7,9,21,27-pentaoxatricyclo[21.3.1.0^{3,8}]heptacosan-25-yl] (~{E})-2-methylbut-2-enoate

ChemComp-SXU:
9-benzyl-1,5-bis(4-methylbenzene-1-sulfonyl)-3-methylidene-1,5,9-triazacyclododecane

ChemComp-SWR:
N'-(4-chlorophenyl)-N-[(4R)-3-(4-chlorophenyl)-5,5-dimethyl-1-(2-{(2E)-2-[(2E)-3-(5-nitrofuran-2-yl)prop-2-en-1-ylidene]hydrazinyl}-2-oxoethyl)-2-oxoimidazolidin-4-yl]-N-hydroxyurea

Source
  • homo sapiens (human)
  • synthetic construct (others)
  • lyngbya bouillonii (bacteria)
  • Saccharomyces cerevisiae (brewer's yeast)
  • Saccharomyces cerevisiae 'var. diastaticus' (brewer's yeast)
KeywordsPROTEIN TRANSPORT/INHIBITOR / translocon / inhibitor / protein translocation / PROTEIN TRANSPORT / PROTEIN TRANSPORT-INHIBITOR complex / decatransin

+
About Yorodumi Papers

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242):Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi Papers

Database of articles cited by EMDB/PDB/SASBDB data

  • Database of articles cited by EMDB, PDB, and SASBDB entries
  • Using PubMed data

Related info.:EMDB / PDB / SASBDB / Yorodumi / EMN Papers / Changes in new EM Navigator and Yorodumi

Read more