[English] 日本語
Yorodumi
- EMDB-2677: Three-dimensional structure of human gamma-secretase at 4.5 angst... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-2677
TitleThree-dimensional structure of human gamma-secretase at 4.5 angstrom resolution
Map dataReconstruction of human gamma-secretase. The particles were selected by one-step of 3D classification. This map has good density for Nicastrin extracellular domain, but slightly worse density for transmembrane domain.
Sample
  • Sample: human gamma-secretase
  • Protein or peptide: human gamma-secretase
Keywordshuman gamma-secretase / cryo EM
Function / homology
Function and homology information


Cajal-Retzius cell differentiation / positive regulation of L-glutamate import across plasma membrane / amyloid precursor protein biosynthetic process / negative regulation of core promoter binding / positive regulation of endopeptidase activity / gamma-secretase complex / aspartic endopeptidase activity, intramembrane cleaving / short-term synaptic potentiation / positive regulation of amyloid precursor protein biosynthetic process / Noncanonical activation of NOTCH3 ...Cajal-Retzius cell differentiation / positive regulation of L-glutamate import across plasma membrane / amyloid precursor protein biosynthetic process / negative regulation of core promoter binding / positive regulation of endopeptidase activity / gamma-secretase complex / aspartic endopeptidase activity, intramembrane cleaving / short-term synaptic potentiation / positive regulation of amyloid precursor protein biosynthetic process / Noncanonical activation of NOTCH3 / protein catabolic process at postsynapse / TGFBR3 PTM regulation / sequestering of calcium ion / Notch receptor processing / synaptic vesicle targeting / positive regulation of coagulation / negative regulation of axonogenesis / central nervous system myelination / membrane protein intracellular domain proteolysis / growth factor receptor binding / T cell activation involved in immune response / skin morphogenesis / choline transport / NOTCH4 Activation and Transmission of Signal to the Nucleus / dorsal/ventral neural tube patterning / neural retina development / regulation of resting membrane potential / myeloid dendritic cell differentiation / L-glutamate import across plasma membrane / Regulated proteolysis of p75NTR / regulation of phosphorylation / metanephros development / locomotion / brain morphogenesis / endoplasmic reticulum calcium ion homeostasis / nuclear outer membrane / amyloid precursor protein metabolic process / regulation of synaptic vesicle cycle / regulation of long-term synaptic potentiation / smooth endoplasmic reticulum calcium ion homeostasis / embryonic limb morphogenesis / regulation of postsynapse organization / astrocyte activation involved in immune response / cell fate specification / regulation of canonical Wnt signaling pathway / skeletal system morphogenesis / aggresome / myeloid cell homeostasis / azurophil granule membrane / G protein-coupled dopamine receptor signaling pathway / glutamate receptor signaling pathway / Hydrolases; Acting on peptide bonds (peptidases); Aspartic endopeptidases / ciliary rootlet / Golgi cisterna membrane / positive regulation of dendritic spine development / positive regulation of amyloid fibril formation / positive regulation of receptor recycling / regulation of neuron projection development / protein glycosylation / blood vessel development / mitochondrial transport / amyloid precursor protein catabolic process / adult behavior / heart looping / cerebral cortex cell migration / amyloid-beta formation / membrane protein ectodomain proteolysis / negative regulation of apoptotic signaling pathway / autophagosome assembly / EPH-ephrin mediated repulsion of cells / negative regulation of ubiquitin-dependent protein catabolic process / endopeptidase activator activity / neuron development / somitogenesis / smooth endoplasmic reticulum / hematopoietic progenitor cell differentiation / Nuclear signaling by ERBB4 / calcium ion homeostasis / T cell proliferation / regulation of synaptic transmission, glutamatergic / rough endoplasmic reticulum / Notch signaling pathway / Degradation of the extracellular matrix / neuron projection maintenance / NOTCH2 Activation and Transmission of Signal to the Nucleus / cerebellum development / cellular response to calcium ion / NRIF signals cell death from the nucleus / Activated NOTCH1 Transmits Signal to the Nucleus / dendritic shaft / thymus development / positive regulation of glycolytic process / epithelial cell proliferation / post-embryonic development / PDZ domain binding / astrocyte activation / NOTCH3 Activation and Transmission of Signal to the Nucleus / apoptotic signaling pathway / synapse organization / neuromuscular junction
Similarity search - Function
Peptidase A22A, presenilin 1 / Gamma-secretase subunit Aph-1 / Gamma-secretase aspartyl protease complex, presenilin enhancer-2 subunit / Aph-1 protein / Presenilin enhancer-2 subunit of gamma secretase / Peptidase A22A, presenilin / Presenilin, C-terminal / Presenilin / Nicastrin / Nicastrin, small lobe ...Peptidase A22A, presenilin 1 / Gamma-secretase subunit Aph-1 / Gamma-secretase aspartyl protease complex, presenilin enhancer-2 subunit / Aph-1 protein / Presenilin enhancer-2 subunit of gamma secretase / Peptidase A22A, presenilin / Presenilin, C-terminal / Presenilin / Nicastrin / Nicastrin, small lobe / Nicastrin large lobe / Nicastrin small lobe / Presenilin/signal peptide peptidase / Presenilin, signal peptide peptidase, family
Similarity search - Domain/homology
Presenilin-1 / Nicastrin / Gamma-secretase subunit APH-1A / Gamma-secretase subunit PEN-2
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / negative staining / Resolution: 4.5 Å
AuthorsLu PL / Bai XC / Ma D / Xie T / Yan CY / Sun LF / Yang GH / Zhao YY / Zhou R / Scheres SHW / Shi YG
CitationJournal: Nature / Year: 2014
Title: Three-dimensional structure of human γ-secretase.
Authors: Peilong Lu / Xiao-Chen Bai / Dan Ma / Tian Xie / Chuangye Yan / Linfeng Sun / Guanghui Yang / Yanyu Zhao / Rui Zhou / Sjors H W Scheres / Yigong Shi /
Abstract: The γ-secretase complex, comprising presenilin 1 (PS1), PEN-2, APH-1 and nicastrin, is a membrane-embedded protease that controls a number of important cellular functions through substrate cleavage. ...The γ-secretase complex, comprising presenilin 1 (PS1), PEN-2, APH-1 and nicastrin, is a membrane-embedded protease that controls a number of important cellular functions through substrate cleavage. Aberrant cleavage of the amyloid precursor protein (APP) results in aggregation of amyloid-β, which accumulates in the brain and consequently causes Alzheimer's disease. Here we report the three-dimensional structure of an intact human γ-secretase complex at 4.5 Å resolution, determined by cryo-electron-microscopy single-particle analysis. The γ-secretase complex comprises a horseshoe-shaped transmembrane domain, which contains 19 transmembrane segments (TMs), and a large extracellular domain (ECD) from nicastrin, which sits immediately above the hollow space formed by the TM horseshoe. Intriguingly, nicastrin ECD is structurally similar to a large family of peptidases exemplified by the glutamate carboxypeptidase PSMA. This structure serves as an important basis for understanding the functional mechanisms of the γ-secretase complex.
History
DepositionJun 14, 2014-
Header (metadata) releaseJun 25, 2014-
Map releaseJul 9, 2014-
UpdateAug 19, 2015-
Current statusAug 19, 2015Processing site: PDBe / Status: Released

-
Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.12
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by radius
  • Surface level: 0.12
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: PDB-5a63
  • Surface level: 0.12
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

EMD-2677.png

Downloads & links

-
Map

FileDownload / File: emd_2677.map.gz / Format: CCP4 / Size: 10.2 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationReconstruction of human gamma-secretase. The particles were selected by one-step of 3D classification. This map has good density for Nicastrin extracellular domain, but slightly worse density for transmembrane domain.
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.76 Å/pix.
x 140 pix.
= 246.4 Å		1.76 Å/pix.
x 140 pix.
= 246.4 Å		1.76 Å/pix.
x 140 pix.
= 246.4 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.76 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.12 / Movie #1: 0.12
Minimum - Maximum-0.24971597 - 0.41268069
Average (Standard dev.)0.00005459 (±0.02389037)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions140140140
Spacing140140140
CellA=B=C: 246.4 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.761.761.76
M x/y/z140140140
origin x/y/z0.0000.0000.000
length x/y/z246.400246.400246.400
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS140140140
D min/max/mean-0.2500.4130.000

-
Supplemental data

-
Supplemental map: emd 2677 additional 1.map

Fileemd_2677_additional_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Supplemental map: emd 2677 half map 1.map

Fileemd_2677_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Supplemental map: emd 2677 half map 2.map

Fileemd_2677_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : human gamma-secretase

EntireName: human gamma-secretase
Components
  • Sample: human gamma-secretase
  • Protein or peptide: human gamma-secretase

-
Supramolecule #1000: human gamma-secretase

SupramoleculeName: human gamma-secretase / type: sample / ID: 1000 / Oligomeric state: tetramer / Number unique components: 1
Molecular weightExperimental: 170 KDa / Theoretical: 170 KDa

-
Macromolecule #1: human gamma-secretase

MacromoleculeName: human gamma-secretase / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Oligomeric state: tetramer / Recombinant expression: Yes
Source (natural)Organism: Homo sapiens (human) / synonym: Human / Cell: HEK 293F
Molecular weightExperimental: 170 KDa / Theoretical: 170 KDa
Recombinant expressionOrganism: Homo sapiens (human) / Recombinant cell: HEK 293F / Recombinant plasmid: pMLink

-
Experimental details

-
Structure determination

Methodnegative staining, cryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration6 mg/mL
BufferpH: 7.4
Details: 25 mM HEPES, pH 7.4, 150 mM NaCl and amphipol A8-35
StainingType: NEGATIVE / Details: cryo-EM
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 90 K / Instrument: FEI VITROBOT MARK IV / Method: Blot for 4S before plunging

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
TemperatureMin: 80 K / Max: 90 K / Average: 85 K
DateFeb 26, 2014
Image recordingCategory: CCD / Film or detector model: GATAN K2 (4k x 4k) / Digitization - Sampling interval: 5 µm / Number real images: 1471 / Average electron dose: 38 e/Å2 / Details: 15 frames were recorded during the imaging.
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsCalibrated magnification: 28409 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 4.4 µm / Nominal defocus min: 1.4 µm / Nominal magnification: 64000
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

CTF correctionDetails: Each particle
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 4.5 Å / Resolution method: OTHER / Software - Name: CTFFIND3, RELION
Details: Use a newly developed statistical movie processing approach to compensate for beam-induced movement.
Number images used: 144545

+
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