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- PDB-8x1c: Structure of nucleosome-bound SRCAP-C in the ADP-bound state -

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Entry
Database: PDB / ID: 8x1c
TitleStructure of nucleosome-bound SRCAP-C in the ADP-bound state
Components
  • (DNA (147-MER)) x 2
  • Actin, cytoplasmic 1
  • Actin-like protein 6A
  • Actin-related protein 6
  • DNA methyltransferase 1-associated protein 1
  • Helicase SRCAP
  • Histone H2A type 1-C
  • Histone H2B type 1-C/E/F/G/I
  • Histone H3.1
  • Histone H4
  • RuvB-like 1
  • RuvB-like 2
  • Vacuolar protein sorting-associated protein 72 homolog
  • YEATS domain-containing protein 4
  • Zinc finger HIT domain-containing protein 1
KeywordsDNA BINDING PROTEIN/DNA / Remodeler / SRCAP / H2A.Z / DNA BINDING PROTEIN-DNA complex
Function / homology
Function and homology information


positive regulation of lymphoid progenitor cell differentiation / modification-dependent protein binding / intestinal stem cell homeostasis / promoter-enhancer loop anchoring activity / telomerase RNA localization to Cajal body / positive regulation of norepinephrine uptake / regulation of DNA strand elongation / positive regulation of telomere maintenance in response to DNA damage / histone chaperone activity / establishment of protein localization to chromatin ...positive regulation of lymphoid progenitor cell differentiation / modification-dependent protein binding / intestinal stem cell homeostasis / promoter-enhancer loop anchoring activity / telomerase RNA localization to Cajal body / positive regulation of norepinephrine uptake / regulation of DNA strand elongation / positive regulation of telomere maintenance in response to DNA damage / histone chaperone activity / establishment of protein localization to chromatin / cellular response to cytochalasin B / R2TP complex / bBAF complex / npBAF complex / regulation of transepithelial transport / nBAF complex / brahma complex / heart process / dynein axonemal particle / morphogenesis of a polarized epithelium / neural retina development / protein localization to adherens junction / postsynaptic actin cytoskeleton / Swr1 complex / structural constituent of postsynaptic actin cytoskeleton / Formation of the dystrophin-glycoprotein complex (DGC) / GBAF complex / Formation of annular gap junctions / Tat protein binding / Gap junction degradation / regulation of G0 to G1 transition / Folding of actin by CCT/TriC / Cell-extracellular matrix interactions / dense body / RPAP3/R2TP/prefoldin-like complex / Activation of the TFAP2 (AP-2) family of transcription factors / Ino80 complex / regulation of nucleotide-excision repair / Prefoldin mediated transfer of substrate to CCT/TriC / RSC-type complex / apical protein localization / muscle cell differentiation / regulation of double-strand break repair / blastocyst formation / box C/D snoRNP assembly / adherens junction assembly / RHOF GTPase cycle / nucleolus organization / Adherens junctions interactions / tight junction / Sensory processing of sound by outer hair cells of the cochlea / positive regulation of DNA damage response, signal transduction by p53 class mediator / protein folding chaperone complex / Interaction between L1 and Ankyrins / SWI/SNF complex / regulation of mitotic metaphase/anaphase transition / Sensory processing of sound by inner hair cells of the cochlea / negative regulation of transcription by RNA polymerase I / positive regulation of T cell differentiation / regulation of norepinephrine uptake / transporter regulator activity / apical junction complex / nitric-oxide synthase binding / positive regulation of double-strand break repair / spinal cord development / maintenance of blood-brain barrier / regulation of chromosome organization / NuA4 histone acetyltransferase complex / establishment or maintenance of cell polarity / cortical cytoskeleton / histone acetyltransferase activity / RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known / positive regulation of transcription by RNA polymerase I / positive regulation of stem cell population maintenance / Regulation of MITF-M-dependent genes involved in pigmentation / Recycling pathway of L1 / regulation of synaptic vesicle endocytosis / regulation of G1/S transition of mitotic cell cycle / regulation of DNA replication / TFIID-class transcription factor complex binding / brush border / regulation of embryonic development / kinesin binding / MLL1 complex / somatic stem cell population maintenance / Telomere Extension By Telomerase / EPH-ephrin mediated repulsion of cells / negative regulation of cell differentiation / RHO GTPases Activate WASPs and WAVEs / positive regulation of transcription initiation by RNA polymerase II / positive regulation of myoblast differentiation / RHO GTPases activate IQGAPs / negative regulation of megakaryocyte differentiation / positive regulation of double-strand break repair via homologous recombination / protein localization to CENP-A containing chromatin / regulation of DNA repair / regulation of protein localization to plasma membrane / Chromatin modifying enzymes / RNA polymerase II core promoter sequence-specific DNA binding / Replacement of protamines by nucleosomes in the male pronucleus
Similarity search - Function
DNA methyltransferase 1-associated 1 / HIT zinc finger / DNA methyltransferase 1-associated protein 1 (DMAP1) / Vps71/ZNHIT1 / SWR1-complex protein 4/DNA methyltransferase 1-associated protein 1 / DAMP1, SANT/Myb-like domain / SANT/Myb-like domain of DAMP1 / Zinc finger HIT-type profile. / YEATS / Zinc finger, HIT-type ...DNA methyltransferase 1-associated 1 / HIT zinc finger / DNA methyltransferase 1-associated protein 1 (DMAP1) / Vps71/ZNHIT1 / SWR1-complex protein 4/DNA methyltransferase 1-associated protein 1 / DAMP1, SANT/Myb-like domain / SANT/Myb-like domain of DAMP1 / Zinc finger HIT-type profile. / YEATS / Zinc finger, HIT-type / Vps72/YL1, N-terminal / YL1 nuclear protein / : / Vps72/YL1, C-terminal / YL1 nuclear protein C-terminal domain / YL1 nuclear protein C-terminal domain / : / YEATS superfamily / YEATS family / YEATS domain profile. / domain in helicases and associated with SANT domains / DNA binding domain with preference for A/T rich regions / RuvB-like / RuvB-like, AAA-lid domain / RuvBL1/2, DNA/RNA binding domain / TIP49 P-loop domain / TIP49 AAA-lid domain / TIP49, P-loop domain / AT hook, DNA-binding motif / HSA domain / Helicase/SANT-associated domain / HSA domain profile. / : / SNF2-like, N-terminal domain superfamily / SNF2, N-terminal / SNF2-related domain / Actins signature 1. / Actin, conserved site / Actins signature 2. / Actin/actin-like conserved site / Actins and actin-related proteins signature. / Actin / Actin family / Actin / : / Histone H2B signature. / Histone H2B / Histone H2B / Histone H2A conserved site / Histone H2A signature. / Histone H2A, C-terminal domain / C-terminus of histone H2A / Histone H2A / Histone 2A / TATA box binding protein associated factor / TATA box binding protein associated factor (TAF), histone-like fold domain / Histone H4, conserved site / Histone H4 signature. / Histone H4 / Histone H4 / CENP-T/Histone H4, histone fold / Centromere kinetochore component CENP-T histone fold / Helicase conserved C-terminal domain / Histone H3 signature 1. / Histone H3 signature 2. / Histone H3 / Histone H3/CENP-A / ATPase, nucleotide binding domain / Histone H2A/H2B/H3 / Core histone H2A/H2B/H3/H4 / Histone-fold / helicase superfamily c-terminal domain / Superfamilies 1 and 2 helicase C-terminal domain profile. / Superfamilies 1 and 2 helicase ATP-binding type-1 domain profile. / DEAD-like helicases superfamily / Helicase, C-terminal / Helicase superfamily 1/2, ATP-binding domain / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
ADENOSINE-5'-DIPHOSPHATE / ADENOSINE-5'-TRIPHOSPHATE / DNA / DNA (> 10) / DNA (> 100) / Zinc finger HIT domain-containing protein 1 / YEATS domain-containing protein 4 / Actin-like protein 6A / Actin, cytoplasmic 1 / Histone H4 ...ADENOSINE-5'-DIPHOSPHATE / ADENOSINE-5'-TRIPHOSPHATE / DNA / DNA (> 10) / DNA (> 100) / Zinc finger HIT domain-containing protein 1 / YEATS domain-containing protein 4 / Actin-like protein 6A / Actin, cytoplasmic 1 / Histone H4 / Histone H2B type 1-C/E/F/G/I / Histone H3.1 / Vacuolar protein sorting-associated protein 72 homolog / Helicase SRCAP / Histone H2A type 1-C / Actin-related protein 6 / DNA methyltransferase 1-associated protein 1 / RuvB-like 2 / RuvB-like 1
Similarity search - Component
Biological speciesHomo sapiens (human)
synthetic construct (others)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å
AuthorsYu, J. / Wang, Q. / Yu, Z. / Li, W. / Wang, L. / Xu, Y.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC) China
CitationJournal: Cell Discov / Year: 2024
Title: Structural insights into histone exchange by human SRCAP complex.
Authors: Jiali Yu / Fengrui Sui / Feng Gu / Wanjun Li / Zishuo Yu / Qianmin Wang / Shuang He / Li Wang / Yanhui Xu /
Abstract: Histone variant H2A.Z is found at promoters and regulates transcription. The ATP-dependent chromatin remodeler SRCAP complex (SRCAP-C) promotes the replacement of canonical histone H2A-H2B dimer with ...Histone variant H2A.Z is found at promoters and regulates transcription. The ATP-dependent chromatin remodeler SRCAP complex (SRCAP-C) promotes the replacement of canonical histone H2A-H2B dimer with H2A.Z-H2B dimer. Here, we determined structures of human SRCAP-C bound to H2A-containing nucleosome at near-atomic resolution. The SRCAP subunit integrates a 6-subunit actin-related protein (ARP) module and an ATPase-containing motor module. The ATPase-associated ARP module encircles half of the nucleosome along the DNA and may restrain net DNA translocation, a unique feature of SRCAP-C. The motor module adopts distinct nucleosome binding modes in the apo (nucleotide-free), ADP-bound, and ADP-BeF-bound states, suggesting that ATPase-driven movement destabilizes H2A-H2B by unwrapping the entry DNA and pulls H2A-H2B out of nucleosome through the ZNHIT1 subunit. Structure-guided chromatin immunoprecipitation sequencing analysis confirmed the requirement of H2A-contacting ZNHIT1 in maintaining H2A.Z occupancy on the genome. Our study provides structural insights into the mechanism of H2A-H2A.Z exchange mediated by SRCAP-C.
History
DepositionNov 6, 2023Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Mar 6, 2024Provider: repository / Type: Initial release
Revision 1.1May 29, 2024Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Histone H2A type 1-C
B: Histone H2B type 1-C/E/F/G/I
C: Histone H3.1
D: Histone H4
E: Histone H2A type 1-C
F: Histone H2B type 1-C/E/F/G/I
G: Histone H3.1
H: Histone H4
I: Helicase SRCAP
J: Vacuolar protein sorting-associated protein 72 homolog
K: Actin-related protein 6
L: Zinc finger HIT domain-containing protein 1
M: RuvB-like 1
N: RuvB-like 2
O: RuvB-like 1
P: RuvB-like 2
Q: RuvB-like 1
R: RuvB-like 2
S: Actin, cytoplasmic 1
T: Actin-like protein 6A
U: Actin, cytoplasmic 1
V: DNA methyltransferase 1-associated protein 1
W: YEATS domain-containing protein 4
X: DNA (147-MER)
Y: DNA (147-MER)
hetero molecules


Theoretical massNumber of molelcules
Total (without water)1,168,33435
Polymers1,163,82225
Non-polymers4,51210
Water00
1


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

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Components

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Protein , 14 types, 23 molecules AEBFCGDHIJKLMOQNPRSUTVW

#1: Protein Histone H2A type 1-C / H2A-clustered histone 6 / Histone H2A/l


Mass: 14135.523 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: H2AC6, H2AFL, HIST1H2AC / Production host: Escherichia coli (E. coli) / References: UniProt: Q93077
#2: Protein Histone H2B type 1-C/E/F/G/I / Histone H2B.1 A / Histone H2B.a / H2B/a / Histone H2B.g / H2B/g / Histone H2B.h / H2B/h / Histone ...Histone H2B.1 A / Histone H2B.a / H2B/a / Histone H2B.g / H2B/g / Histone H2B.h / H2B/h / Histone H2B.k / H2B/k / Histone H2B.l / H2B/l


Mass: 13937.213 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human)
Gene: H2BC4, H2BFL, HIST1H2BC, H2BC6, H2BFH, HIST1H2BE, H2BC7, H2BFG, HIST1H2BF, H2BC8, H2BFA, HIST1H2BG, H2BC10, H2BFK, HIST1H2BI
Production host: Escherichia coli (E. coli) / References: UniProt: P62807
#3: Protein Histone H3.1 / Histone H3/a / Histone H3/b / Histone H3/c / Histone H3/d / Histone H3/f / Histone H3/h / Histone ...Histone H3/a / Histone H3/b / Histone H3/c / Histone H3/d / Histone H3/f / Histone H3/h / Histone H3/i / Histone H3/j / Histone H3/k / Histone H3/l


Mass: 15437.167 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human)
Gene: H3C1, H3FA, HIST1H3A, H3C2, H3FL, HIST1H3B, H3C3, H3FC HIST1H3C, H3C4, H3FB, HIST1H3D, H3C6, H3FD, HIST1H3E, H3C7, H3FI, HIST1H3F, H3C8, H3FH, HIST1H3G, H3C10, H3FK, HIST1H3H, H3C11, H3FF, ...Gene: H3C1, H3FA, HIST1H3A, H3C2, H3FL, HIST1H3B, H3C3, H3FC HIST1H3C, H3C4, H3FB, HIST1H3D, H3C6, H3FD, HIST1H3E, H3C7, H3FI, HIST1H3F, H3C8, H3FH, HIST1H3G, H3C10, H3FK, HIST1H3H, H3C11, H3FF, HIST1H3I, H3C12, H3FJ, HIST1H3J
Production host: Escherichia coli (E. coli) / References: UniProt: P68431
#4: Protein Histone H4


Mass: 11394.426 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human)
Gene: H4C1, H4/A, H4FA, HIST1H4A, H4C2, H4/I, H4FI, HIST1H4B, H4C3, H4/G, H4FG, HIST1H4C, H4C4, H4/B, H4FB, HIST1H4D, H4C5, H4/J, H4FJ, HIST1H4E, H4C6, H4/C, H4FC, HIST1H4F, H4C8, H4/H, H4FH, ...Gene: H4C1, H4/A, H4FA, HIST1H4A, H4C2, H4/I, H4FI, HIST1H4B, H4C3, H4/G, H4FG, HIST1H4C, H4C4, H4/B, H4FB, HIST1H4D, H4C5, H4/J, H4FJ, HIST1H4E, H4C6, H4/C, H4FC, HIST1H4F, H4C8, H4/H, H4FH, HIST1H4H, H4C9, H4/M, H4FM, HIST1H4I, H4C11, H4/E, H4FE, HIST1H4J, H4C12, H4/D, H4FD, HIST1H4K, H4C13, H4/K, H4FK, HIST1H4L, H4C14, H4/N, H4F2, H4FN, HIST2H4, HIST2H4A, H4C15, H4/O, H4FO, HIST2H4B, H4C16, H4-16, HIST4H4
Production host: Escherichia coli (E. coli) / References: UniProt: P62805
#5: Protein Helicase SRCAP / Domino homolog 2 / Snf2-related CBP activator


Mass: 343915.250 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SRCAP, KIAA0309 / Production host: Homo sapiens (human)
References: UniProt: Q6ZRS2, Hydrolases; Acting on acid anhydrides; Acting on acid anhydrides to facilitate cellular and subcellular movement
#6: Protein Vacuolar protein sorting-associated protein 72 homolog / Protein YL-1 / Transcription factor-like 1


Mass: 40658.363 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: VPS72, TCFL1, YL1 / Production host: Homo sapiens (human) / References: UniProt: Q15906
#7: Protein Actin-related protein 6 / hArp6 / hARPX


Mass: 45857.902 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ACTR6, CDA12 / Production host: Homo sapiens (human) / References: UniProt: Q9GZN1
#8: Protein Zinc finger HIT domain-containing protein 1 / Cyclin-G1-binding protein 1 / Zinc finger protein subfamily 4A member 1 / p18 Hamlet


Mass: 17567.023 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ZNHIT1, CGBP1, ZNFN4A1 / Production host: Homo sapiens (human) / References: UniProt: O43257
#9: Protein RuvB-like 1 / 49 kDa TATA box-binding protein-interacting protein / 49 kDa TBP-interacting protein / 54 kDa ...49 kDa TATA box-binding protein-interacting protein / 49 kDa TBP-interacting protein / 54 kDa erythrocyte cytosolic protein / ECP-54 / INO80 complex subunit H / Nuclear matrix protein 238 / NMP 238 / Pontin 52 / TIP49a / TIP60-associated protein 54-alpha / TAP54-alpha


Mass: 50296.914 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: RUVBL1, INO80H, NMP238, TIP49, TIP49A / Production host: Homo sapiens (human) / References: UniProt: Q9Y265, DNA helicase
#10: Protein RuvB-like 2 / 48 kDa TATA box-binding protein-interacting protein / 48 kDa TBP-interacting protein / 51 kDa ...48 kDa TATA box-binding protein-interacting protein / 48 kDa TBP-interacting protein / 51 kDa erythrocyte cytosolic protein / ECP-51 / INO80 complex subunit J / Repressing pontin 52 / Reptin 52 / TIP49b / TIP60-associated protein 54-beta / TAP54-beta


Mass: 51222.465 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: RUVBL2, INO80J, TIP48, TIP49B, CGI-46 / Production host: Homo sapiens (human) / References: UniProt: Q9Y230, DNA helicase
#11: Protein Actin, cytoplasmic 1 / Beta-actin


Mass: 41782.660 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ACTB / Production host: Homo sapiens (human)
References: UniProt: P60709, Hydrolases; Acting on acid anhydrides; Acting on acid anhydrides to facilitate cellular and subcellular movement
#12: Protein Actin-like protein 6A / 53 kDa BRG1-associated factor A / Actin-related protein Baf53a / ArpNbeta / BRG1-associated factor ...53 kDa BRG1-associated factor A / Actin-related protein Baf53a / ArpNbeta / BRG1-associated factor 53A / BAF53A / INO80 complex subunit K


Mass: 47509.812 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ACTL6A, BAF53, BAF53A, INO80K / Production host: Homo sapiens (human) / References: UniProt: O96019
#13: Protein DNA methyltransferase 1-associated protein 1 / DNMAP1 / DNMT1-associated protein 1


Mass: 53090.699 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: DMAP1, KIAA1425 / Production host: Homo sapiens (human) / References: UniProt: Q9NPF5
#14: Protein YEATS domain-containing protein 4 / Glioma-amplified sequence 41 / Gas41 / NuMA-binding protein 1 / NuBI-1 / NuBI1


Mass: 26541.537 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: YEATS4, GAS41 / Production host: Homo sapiens (human) / References: UniProt: O95619

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DNA chain , 2 types, 2 molecules XY

#15: DNA chain DNA (147-MER)


Mass: 45644.070 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others)
#16: DNA chain DNA (147-MER)


Mass: 45105.727 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others)

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Non-polymers , 2 types, 10 molecules

#17: Chemical
ChemComp-ADP / ADENOSINE-5'-DIPHOSPHATE


Mass: 427.201 Da / Num. of mol.: 7 / Source method: obtained synthetically / Formula: C10H15N5O10P2 / Feature type: SUBJECT OF INVESTIGATION / Comment: ADP, energy-carrying molecule*YM
#18: Chemical ChemComp-ATP / ADENOSINE-5'-TRIPHOSPHATE


Mass: 507.181 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C10H16N5O13P3 / Comment: ATP, energy-carrying molecule*YM

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Details

Has ligand of interestY

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Experimental details

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Experiment

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

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Sample preparation

ComponentName: Structure of nucleosome-bound SRCAP-C in the ADP-bound state
Type: COMPLEX / Entity ID: #1-#16 / Source: MULTIPLE SOURCES
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 8
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 1500 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 555303 / Symmetry type: POINT

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