[English] 日本語
Yorodumi
- PDB-9yws: Human Sec61 complex bound to coibamide A -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9yws
TitleHuman Sec61 complex bound to coibamide A
Components
  • Coibamide A
  • Protein transport protein Sec61 subunit alpha isoform 1
  • Protein transport protein Sec61 subunit beta
  • Protein transport protein Sec61 subunit gamma
KeywordsPROTEIN TRANSPORT / Sec61 / Coibamide / Endoplasmic reticulum / depsipeptide
Function / homology
Function and homology information


endoplasmic reticulum Sec complex / pronephric nephron development / cotranslational protein targeting to membrane / endoplasmic reticulum quality control compartment / Ssh1 translocon complex / Sec61 translocon complex / protein insertion into ER membrane / post-translational protein targeting to endoplasmic reticulum membrane / protein targeting to ER / post-translational protein targeting to membrane, translocation ...endoplasmic reticulum Sec complex / pronephric nephron development / cotranslational protein targeting to membrane / endoplasmic reticulum quality control compartment / Ssh1 translocon complex / Sec61 translocon complex / protein insertion into ER membrane / post-translational protein targeting to endoplasmic reticulum membrane / protein targeting to ER / post-translational protein targeting to membrane, translocation / SRP-dependent cotranslational protein targeting to membrane, translocation / endoplasmic reticulum organization / SRP-dependent cotranslational protein targeting to membrane / signal sequence receptor activity / epidermal growth factor binding / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / retrograde protein transport, ER to cytosol / transmembrane protein transporter activity / SRP-dependent cotranslational protein targeting to membrane / ERAD pathway / response to type II interferon / guanyl-nucleotide exchange factor activity / calcium channel activity / ribosome binding / ER-Phagosome pathway / endoplasmic reticulum membrane / endoplasmic reticulum / RNA binding / membrane / cytosol
Similarity search - Function
Protein transport Sec61-beta/Sbh / Protein transport protein SecG/Sec61-beta/Sbh / Sec61beta family / Protein translocase SEC61 complex, gamma subunit / Protein translocase SecE domain superfamily / Translocon Sec61/SecY, plug domain / Plug domain of Sec61p / Protein secE/sec61-gamma signature. / Protein secY signature 1. / Protein secY signature 2. ...Protein transport Sec61-beta/Sbh / Protein transport protein SecG/Sec61-beta/Sbh / Sec61beta family / Protein translocase SEC61 complex, gamma subunit / Protein translocase SecE domain superfamily / Translocon Sec61/SecY, plug domain / Plug domain of Sec61p / Protein secE/sec61-gamma signature. / Protein secY signature 1. / Protein secY signature 2. / SecE/Sec61-gamma subunits of protein translocation complex / Protein translocase complex, SecE/Sec61-gamma subunit / SecY/SEC61-alpha family / SecY domain superfamily / SecY conserved site / SecY
Similarity search - Domain/homology
CHOLESTEROL / Protein transport protein Sec61 subunit gamma / Protein transport protein Sec61 subunit beta / Protein transport protein Sec61 subunit alpha isoform 1
Similarity search - Component
Biological speciesHomo sapiens (human)
Leptolyngbya sp. (bacteria)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.1 Å
AuthorsPark, E. / Wang, L.
Funding support1items
OrganizationGrant numberCountry
Other private
CitationJournal: Cell Chem Biol / Year: 2026
Title: Structure-based design of Sec61 translocon targeting prodrugs minimize off-target toxicity.
Authors: Qingqing Hao / Laurie Wang / Hui Pan / Xihui Xiao / Wenyan Dong / Wencong Pan / Jingjing Sun / Wu Su / Lijing Fang / Eunyong Park / Guiyang Yao /
Abstract: Coibamide A (CbA) is a cyclic depsipeptide that inhibits the function of the Sec61 translocon and exhibits significant antitumor activity. However, its broad Sec61 inhibition results in non-selective ...Coibamide A (CbA) is a cyclic depsipeptide that inhibits the function of the Sec61 translocon and exhibits significant antitumor activity. However, its broad Sec61 inhibition results in non-selective cytotoxicity, limiting therapeutic applications. To elucidate the molecular mechanism of CbA-mediated Sec61 blockade and enable rational prodrug design, we determined the cryo-EM structure of human Sec61 bound to CbA at 3.1 Å resolution. The structure reveals that CbA adopts a distinctive lasso-like conformation and occupies the lateral gate of Sec61, a binding site shared with other Sec61 inhibitors, while forming a particularly more expansive set of interactions with the lateral gate. Guided by these structural insights, we conducted structure-activity relationship studies and developed prodrug strategies that modulate CbA's antitumor activity through the controlled perturbation of intramolecular and protein hydrogen bonding interactions. Together, these results establish a structure-guided strategy for prodrug design of CbA and demonstrate the general applicability of backbone-caging to enhance the tolerability of Sec61 inhibitors.
History
DepositionOct 25, 2025Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 22, 2026Provider: repository / Type: Initial release
Revision 1.0Jul 22, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Jul 22, 2026Data content type: Additional map / Part number: 1 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0Jul 22, 2026Data content type: FSC / Data content type: FSC / Provider: repository / Type: Initial release
Revision 1.0Jul 22, 2026Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jul 22, 2026Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jul 22, 2026Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Jul 22, 2026Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
B: Protein transport protein Sec61 subunit gamma
C: Protein transport protein Sec61 subunit beta
A: Protein transport protein Sec61 subunit alpha isoform 1
D: Coibamide A
hetero molecules


Theoretical massNumber of molelcules
Total (without water)71,6355
Polymers71,2484
Non-polymers3871
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

#1: Protein Protein transport protein Sec61 subunit gamma


Mass: 7752.325 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SEC61G / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P60059
#2: Protein Protein transport protein Sec61 subunit beta


Mass: 9987.456 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SEC61B / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P60468
#3: Protein Protein transport protein Sec61 subunit alpha isoform 1 / Sec61 alpha-1


Mass: 52202.438 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: Two cytosolic loops (263-278 and 394-411) are replaced with the homologous segments of the yeast (S. cerevisiae) Sec61 protein.
Source: (gene. exp.) Homo sapiens (human) / Gene: SEC61A1, SEC61A / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P61619
#4: Protein/peptide Coibamide A


Mass: 1305.642 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Leptolyngbya sp. (bacteria)
#5: Chemical ChemComp-CLR / CHOLESTEROL


Mass: 386.654 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C27H46O
Has ligand of interestY
Has protein modificationY
Sequence detailsTwo cytosolic loops (263-278 and 394-411) in the alpha subunit are replaced with the homologous ...Two cytosolic loops (263-278 and 394-411) in the alpha subunit are replaced with the homologous segments of the yeast (S. cerevisiae) Sec61 protein.

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

Component
IDNameTypeEntity IDParent-IDSource
1Chimeric (human-yeast) Sec complex bound to coibamide ACOMPLEX#1-#40MULTIPLE SOURCES
2Chimeric (human-yeast) Sec complexCOMPLEX#1-#31RECOMBINANT
3coibamide ACOMPLEX#41SYNTHETIC
Molecular weightExperimental value: NO
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
22Homo sapiens (human)9606
33Leptolyngbya sp. (bacteria)47254
Source (recombinant)Organism: Spodoptera frugiperda (fall armyworm)
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 1600 nm / Nominal defocus min: 800 nm
Image recordingAverage exposure time: 6.8 sec. / Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)
EM imaging opticsEnergyfilter name: GIF Quantum LS / Energyfilter slit width: 20 eV

-
Processing

EM software
IDNameVersionCategory
1Warpparticle selection
2cryoSPARCparticle selection
3Topazparticle selection
4SerialEM4.1image acquisition
6cryoSPARC4.7CTF correction
12cryoSPARC4.7initial Euler assignment
13cryoSPARC4.7final Euler assignment
15cryoSPARC4.73D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 284979 / Symmetry type: POINT
RefinementHighest resolution: 3.1 Å
Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0044494
ELECTRON MICROSCOPYf_angle_d0.6616097
ELECTRON MICROSCOPYf_dihedral_angle_d5.352668
ELECTRON MICROSCOPYf_chiral_restr0.04721
ELECTRON MICROSCOPYf_plane_restr0.004753

+
About Yorodumi

-
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

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more