[English] 日本語
Yorodumi
- EMDB-53233: Human dysferlin (1-2017) in the lipid-free, Ca2+-bound state -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-53233
TitleHuman dysferlin (1-2017) in the lipid-free, Ca2+-bound state
Map dataHuman dysferlin (1-2017) in the lipid-free, Ca2 -bound state, overall map (map M2)
Sample
  • Complex: Lipid-free human dysferlin (1-2017) in the Ca2+-bound state
    • Protein or peptide: Dysferlin
  • Ligand: CALCIUM ION
KeywordsFerlins / dysferlin / multi-C2 domains / lipid nanodisc / MEMBRANE PROTEIN
Function / homology
Function and homology information


monocyte activation involved in immune response / regulation of neurotransmitter secretion / calcium-dependent phospholipid binding / macrophage activation involved in immune response / negative regulation of phagocytosis / endocytic vesicle / Smooth Muscle Contraction / T-tubule / cytoplasmic vesicle membrane / sarcolemma ...monocyte activation involved in immune response / regulation of neurotransmitter secretion / calcium-dependent phospholipid binding / macrophage activation involved in immune response / negative regulation of phagocytosis / endocytic vesicle / Smooth Muscle Contraction / T-tubule / cytoplasmic vesicle membrane / sarcolemma / phospholipid binding / centriolar satellite / synaptic vesicle membrane / late endosome / early endosome / endosome / calcium ion binding / extracellular exosome / plasma membrane
Similarity search - Function
Ferlin A-domain / FerA (NUC095) domain / FerA / Ferlin B-domain / FerIin domain / Ferlin, C-terminal domain / Ferlin, second C2 domain / Ferlin family / Ferlin, third C2 domain / Ferlin, fourth C2 domain ...Ferlin A-domain / FerA (NUC095) domain / FerA / Ferlin B-domain / FerIin domain / Ferlin, C-terminal domain / Ferlin, second C2 domain / Ferlin family / Ferlin, third C2 domain / Ferlin, fourth C2 domain / Ferlin, fifth C2 domain / Ferlin, sixth C2 domain / Ferlin, first C2 domain / : / FerB (NUC096) domain / FerI (NUC094) domain / Ferlin C-terminus / Ferlin dsRNA-binding domain-like domain / FerB / FerI / Peroxin/Ferlin domain / Dysferlin domain, N-terminal region. / Dysferlin domain, C-terminal region. / Protein kinase C conserved region 2 (CalB) / C2 domain / C2 domain / C2 domain profile. / C2 domain superfamily
Similarity search - Domain/homology
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.54 Å
AuthorsCretu C / Moser T
Funding support Germany, 1 items
OrganizationGrant numberCountry
German Research Foundation (DFG)CR 937/2-1 and EXC 2067/1-390729940 Germany
CitationJournal: EMBO J / Year: 2025
Title: Structural insights into lipid membrane binding by human ferlins.
Authors: Constantin Cretu / Aleksandar Chernev / Csaba Zoltán Kibédi Szabó / Vladimir Pena / Henning Urlaub / Tobias Moser / Julia Preobraschenski /
Abstract: Ferlins are ancient membrane proteins with a unique architecture, and play central roles in crucial processes that involve Ca-dependent vesicle fusion. Despite their links to multiple human diseases ...Ferlins are ancient membrane proteins with a unique architecture, and play central roles in crucial processes that involve Ca-dependent vesicle fusion. Despite their links to multiple human diseases and numerous functional studies, a mechanistic understanding of how these multi-C domain-containing proteins interact with lipid membranes to promote membrane remodelling and fusion is currently lacking. Here we obtain near-complete cryo-electron microscopy structures of human myoferlin and dysferlin in their Ca- and lipid-bound states. We show that ferlins adopt compact, ring-like tertiary structures upon membrane binding. The top arch of the ferlin ring, composed of the CC-CD region, is rigid and exhibits only little variability across the observed functional states. In contrast, the N-terminal CB and the C-terminal CF-CG domains cycle between alternative conformations and, in response to Ca, close the ferlin ring, promoting tight interaction with the target membrane. Probing key domain interfaces validates the observed architecture, and informs a model of how ferlins engage lipid bilayers in a Ca-dependent manner. This work reveals the general principles of human ferlin structures and provides a framework for future analyses of ferlin-dependent cellular functions and disease mechanisms.
History
DepositionMar 21, 2025-
Header (metadata) releaseJun 4, 2025-
Map releaseJun 4, 2025-
UpdateJul 23, 2025-
Current statusJul 23, 2025Processing site: PDBe / Status: Released

-
Structure visualization

Supplemental images

emd_53233.png

Downloads & links

-
Map

FileDownload / File: emd_53233.map.gz / Format: CCP4 / Size: 282.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationHuman dysferlin (1-2017) in the lipid-free, Ca2 -bound state, overall map (map M2)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.72 Å/pix.
x 420 pix.
= 302.4 Å		0.72 Å/pix.
x 420 pix.
= 302.4 Å		0.72 Å/pix.
x 420 pix.
= 302.4 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.72 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.035
Minimum - Maximum-0.21287283 - 0.34181705
Average (Standard dev.)-0.00012494714 (±0.006754012)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions420420420
Spacing420420420
CellA=B=C: 302.40002 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Mask #1

Fileemd_53233_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Additional map: Human dysferlin (1-2017) in the lipid-free, Ca2 -bound...

Fileemd_53233_additional_1.map
AnnotationHuman dysferlin (1-2017) in the lipid-free, Ca2 -bound state, Fercore map (map M1)
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Additional map: Human dysferlin (1-2017) in the lipid-free, Ca2 -bound...

Fileemd_53233_additional_2.map
AnnotationHuman dysferlin (1-2017) in the lipid-free, Ca2 -bound state, locally scaled map (related to map M2)
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: Human dysferlin (1-2017) in the lipid-free, Ca2 -bound...

Fileemd_53233_half_map_1.map
AnnotationHuman dysferlin (1-2017) in the lipid-free, Ca2 -bound state, half map A (related to map M2)
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: Human dysferlin (1-2017) in the lipid-free, Ca2 -bound...

Fileemd_53233_half_map_2.map
AnnotationHuman dysferlin (1-2017) in the lipid-free, Ca2 -bound state, half map B (related to map M2)
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Lipid-free human dysferlin (1-2017) in the Ca2+-bound state

EntireName: Lipid-free human dysferlin (1-2017) in the Ca2+-bound state
Components
  • Complex: Lipid-free human dysferlin (1-2017) in the Ca2+-bound state
    • Protein or peptide: Dysferlin
  • Ligand: CALCIUM ION

-
Supramolecule #1: Lipid-free human dysferlin (1-2017) in the Ca2+-bound state

SupramoleculeName: Lipid-free human dysferlin (1-2017) in the Ca2+-bound state
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Dysferlin

MacromoleculeName: Dysferlin / type: protein_or_peptide / ID: 1
Details: Cytosolic domain of human dysferlin (residues 1-2017), cloned in frame with an N-terminal twin-StrepII affinity tag.
Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 234.383266 KDa
Recombinant expressionOrganism: Trichoplusia ni (cabbage looper)
SequenceString: MASWSHPQFE KGGGSGGGSG GGSWSHPQFE KLEVLFQGPG SGGGSGGMLR VFILYAENVH TPDTDISDAY CSAVFAGVKK RTKVIKNSV NPVWNEGFEW DLKGIPLDQG SELHVVVKDH ETMGRNRFLG EAKVPLREVL ATPSLSASFN APLLDTKKQP T GASLVLQV ...String:
MASWSHPQFE KGGGSGGGSG GGSWSHPQFE KLEVLFQGPG SGGGSGGMLR VFILYAENVH TPDTDISDAY CSAVFAGVKK RTKVIKNSV NPVWNEGFEW DLKGIPLDQG SELHVVVKDH ETMGRNRFLG EAKVPLREVL ATPSLSASFN APLLDTKKQP T GASLVLQV SYTPLPGAVP LFPPPTPLEP SPTLPDLDVV ADTGGEEDTE DQGLTGDEAE PFLDQSGGPG APTTPRKLPS RP PPHYPGI KRKRSAPTSR KLLSDKPQDF QIRVQVIEGR QLPGVNIKPV VKVTAAGQTK RTRIHKGNSP LFNETLFFNL FDS PGELFD EPIFITVVDS RSLRTDALLG EFRMDVGTIY REPRHAYLRK WLLLSDPDDF SAGARGYLKT SLCVLGPGDE APLE RKDPS EDKEDIESNL LRPTGVALRG AHFCLKVFRA EDLPQMDDAV MDNVKQIFGF ESNKKNLVDP FVEVSFAGKM LCSKI LEKT ANPQWNQNIT LPAMFPSMCE KMRIRIIDWD RLTHNDIVAT TYLSMSKISA PGGEIEEEPA GAVKPSKASD LDDYLG FLP TFGPCYINLY GSPREFTGFP DPYTELNTGK GEGVAYRGRL LLSLETKLVE HSEQKVEDLP ADDILRVEKY LRRRKYS LF AAFYSATMLQ DVDDAIQFEV SIGNYGNKFD MTCLPLASTT QYSRAVFDGC HYYYLPWGNV KPVVVLSSYW EDISHRIE T QNQLLGIADR LEAGLEQVHL ALKAQCSTED VDSLVAQLTD ELIAGCSQPL GDIHETPSAT HLDQYLYQLR THHLSQITE AALALKLGHS ELPAALEQAE DWLLRLRALA EEPQNSLPDI VIWMLQGDKR VAYQRVPAHQ VLFSRRGANY CGKNCGKLQT IFLKYPMEK VPGARMPVQI RVKLWFGLSV DEKEFNQFAE GKLSVFAETY ENETKLALVG NWGTTGLTYP KFSDVTGKIK L PKDSFRPS AGWTWAGDWF VCPEKTLLHD MDAGHLSFVE EVFENQTRLP GGQWIYMSDN YTDVNGEKVL PKDDIECPLG WK WEDEEWS TDLNRAVDEQ GWEYSITIPP ERKPKHWVPA EKMYYTHRRR RWVRLRRRDL SQMEALKRHR QAEAEGEGWE YAS LFGWKF HLEYRKTDAF RRRRWRRRME PLEKTGPAAV FALEGALGGV MDDKSEDSMS VSTLSFGVNR PTISCIFDYG NRYH LRCYM YQARDLAAMD KDSFSDPYAI VSFLHQSQKT VVVKNTLNPT WDQTLIFYEI EIFGEPATVA EQPPSIVVEL YDHDT YGAD EFMGRCICQP SLERMPRLAW FPLTRGSQPS GELLASFELI QREKPAIHHI PGFEVQETSR ILDESEDTDL PYPPPQ REA NIYMVPQNIK PALQRTAIEI LAWGLRNMKS YQLANISSPS LVVECGGQTV QSCVIRNLRK NPNFDICTLF MEVMLPR EE LYCPPITVKV IDNRQFGRRP VVGQCTIRSL ESFLCDPYSA ESPSPQGGPD DVSLLSPGED VLIDIDDKEP LIPIQEEE F IDWWSKFFAS IGEREKCGSY LEKDFDTLKV YDTQLENVEA FEGLSDFCNT FKLYRGKTQE ETEDPSVIGE FKGLFKIYP LPEDPAIPMP PRQFHQLAAQ GPQECLVRIY IVRAFGLQPK DPNGKCDPYI KISIGKKSVS DQDNYIPCTL EPVFGKMFEL TCTLPLEKD LKITLYDYDL LSKDEKIGET VVDLENRLLS KFGARCGLPQ TYCVSGPNQW RDQLRPSQLL HLFCQQHRVK A PVYRTDRV MFQDKEYSIE EIEAGRIPNP HLGPVEERLA LHVLQQQGLV PEHVESRPLY SPLQPDIEQG KLQMWVDLFP KA LGRPGPP FNITPRRARR FFLRCIIWNT RDVILDDLSL TGEKMSDIYV KGWMIGFEEH KQKTDVHYRS LGGEGNFNWR FIF PFDYLP AEQVCTIAKK DAFWRLDKTE SKIPARVVFQ IWDNDKFSFD DFLGSLQLDL NRMPKPAKTA KKCSLDQLDD AFHP EWFVS LFEQKTVKGW WPCVAEEGEK KILAGKLEMT LEIVAESEHE ERPAGQGRDE PNMNPKLED

UniProtKB: Dysferlin

-
Macromolecule #2: CALCIUM ION

MacromoleculeName: CALCIUM ION / type: ligand / ID: 2 / Number of copies: 6 / Formula: CA
Molecular weightTheoretical: 40.078 Da

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration1.08 mg/mL
BufferpH: 7.5
Component:
ConcentrationFormulaName
20.0 mMHEPES4-(2-Hydroxyethyl)-1-piperazine ethanesulfonic acid
150.0 mMKClpotassium chloride
2.5 % (v/v)C3H8O3glycerol
1.0 mMDTTDithiothreitol
1.0 mMCaCl2calcium chloride
GridModel: UltrAuFoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: GOLD / Support film - topology: HOLEY / Pretreatment - Type: PLASMA CLEANING / Pretreatment - Time: 60 sec. / Pretreatment - Atmosphere: AIR
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV
DetailsPrior to cryo-EM grid preparation, the sample was subjected to GraFix, in the presence of 1 mM CaCl2, buffer exchanged and concentrated to A280~1.08. After the application of 3 uL sample, the grid was blotted for 3 s at a blot force of 5 and frozen in liquid ethane cooled by liquid nitrogen.

-
Electron microscopy

MicroscopeTFS KRIOS
Specialist opticsEnergy filter - Name: TFS Selectris / Energy filter - Slit width: 15 eV
Details: Energy filter slit width was set to either 15 eV (Dataset 1) or 10 eV (Dataset 2)
SoftwareName: EPU
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Number grids imaged: 1 / Number real images: 15910 / Average exposure time: 3.01 sec. / Average electron dose: 40.184 e/Å2
Details: Two datasets were collected from the same grid: (i) Dataset 1: 8641 movies, 4582 movies were accepted after curation, total fluence on sample 40.184 e-/A2 (3.01 s per exposure) (ii) Dataset ...Details: Two datasets were collected from the same grid: (i) Dataset 1: 8641 movies, 4582 movies were accepted after curation, total fluence on sample 40.184 e-/A2 (3.01 s per exposure) (ii) Dataset 2: 7269 movies, 4727 movies were accepted after curation, total fluence on sample 40.227 e-/A2 (2.96 s per exposure)
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.3000000000000003 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 165000
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

Particle selectionNumber selected: 2861382
CTF correctionSoftware - Name: cryoSPARC (ver. v.4.1) / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: OTHER / Details: Ab initio reconstruction (in cryoSPARC)
Final reconstructionNumber classes used: 1 / Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.54 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. v.4.1) / Number images used: 29793
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. v.4.1)
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. v.4.1)
Final 3D classificationNumber classes: 4 / Software - Name: RELION (ver. v.4.0)
Details: Focused 3D classification without image alignment (K=4) and a soft mask applied to the C2B-C2E-C2F region.
FSC plot (resolution estimation)

-
Atomic model buiding 1

Initial modelChain - Source name: AlphaFold / Chain - Initial model type: in silico model
SoftwareName: UCSF Chimera (ver. v.1.16)
RefinementSpace: REAL / Protocol: AB INITIO MODEL / Overall B value: 162.24
Output model

PDB-9qls:
Human dysferlin (1-2017) in the lipid-free, Ca2+-bound state

+
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