[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

TitleStructure and function of otoferlin, a synaptic protein of sensory hair cells essential for hearing.
Journal, issue, pagesSci Adv, Vol. 11, Issue 42, Page eady8532, Year 2025
Publish dateOct 17, 2025
AuthorsHan Chen / Constantin Cretu / Abigail Trebilcock / Natalia Evdokimova / Norbert Babai / Laura Feldmann / Florian Leidner / Fritz Benseler / Sophia Mutschall / Klara Esch / Csaba Zoltan Kibedi Szabo / Vladimir Pena / Constantin Pape / Helmut Grubmüller / Nicola Strenzke / Nils Brose / Carolin Wichmann / Julia Preobraschenski / Tobias Moser /
PubMed AbstractHearing relies upon speedy synaptic transmission of sound information from inner hair cells (IHCs) to spiral ganglion neurons. To accomplish this, IHCs use a sophisticated presynaptic machinery ...Hearing relies upon speedy synaptic transmission of sound information from inner hair cells (IHCs) to spiral ganglion neurons. To accomplish this, IHCs use a sophisticated presynaptic machinery including the multi-C domain protein otoferlin that is affected by human deafness mutations. Otoferlin is essential for IHC exocytosis, but how it binds Ca and the target membrane to serve synaptic vesicle (SV) tethering, docking, and fusion remained unclear. Here, we obtained cryo-electron microscopy structures of otoferlin and employed molecular dynamics simulations of membrane binding. We show that membrane binding by otoferlin involves CB-CG domains and repositions CF and CG domains. Disruption of Ca-binding sites of the CD domain in mice altered synaptic sound encoding and eliminated the Ca cooperativity of IHC exocytosis, indicating that it requires the binding of several Ca-ions by otoferlin. Together, our findings elucidate molecular mechanisms underlying otoferlin-mediated SV docking and support the role of otoferlin as Ca sensor of SV fusion in IHCs.
External linksSci Adv / PubMed:41091875 / PubMed Central
MethodsEM (single particle)
Resolution2.23 - 3.43 Å
Structure data

53046

9qe2

EMDB-53046, PDB-9qe2:
Mouse otoferlin (216-1931) in complex with an MSP2N2 lipid nanodisc (30 mol% DOPS, 10 mol% PI(4,5)P2)
Method: EM (single particle) / Resolution: 2.3 Å

54802

9se5

EMDB-54802, PDB-9se5:
Mouse otoferlin (216-1931) in the lipid-free, Ca2+-bound state, "open" conformation (class 2)
Method: EM (single particle) / Resolution: 3.43 Å

54805

9sea

EMDB-54805, PDB-9sea:
Mouse otoferlin (216-1931) in complex with a lipid nanodisc (comprising 25% PS and 5% PIP2)
Method: EM (single particle) / Resolution: 2.23 Å

54809

9seg

EMDB-54809, PDB-9seg:
Mouse otoferlin (216-1931) in the lipid-free Ca2+-bound state, "open" conformation (class 1)
Method: EM (single particle) / Resolution: 2.91 Å

54827

9sfl

EMDB-54827, PDB-9sfl:
Mouse otoferlin (residues 216-1931) in the lipid-bound state (merged datasets)
Method: EM (single particle) / Resolution: 2.27 Å

54883

9sh0

EMDB-54883, PDB-9sh0:
Mouse otoferlin (216-1931) in the lipid-free, Ca2+-free state ("loose" conformation)
Method: EM (single particle) / Resolution: 3.43 Å

54923

9si1

EMDB-54923, PDB-9si1:
Mouse otoferlin (216-1931) in the lipid-free Ca2+-bound state, "closed-like" conformation
Method: EM (single particle) / Resolution: 3.1 Å

Chemicals

ChemComp-CA:
Unknown entry

ChemComp-PSF:
1,2-DICAPROYL-SN-PHOSPHATIDYL-L-SERINE

ChemComp-HOH:
WATER

Source
  • mus musculus (house mouse)
KeywordsMEMBRANE PROTEIN / Ferlins / otoferlin / lipid nanodisc / synaptic vesicle / exocytosis / auditory nerve / deafness / multi-C2 domain / Ferlin / Ca2+-binding / membrane fusion

+
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