[English] 日本語
Yorodumi
- EMDB-11382: two-protofilament amyloid structure of S20G variant of human amyl... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-11382
Titletwo-protofilament amyloid structure of S20G variant of human amylin (IAPP - islet amyloid polypeptide)
Map data
Sample
  • Complex: two-protofilament amyloid fibrils of S20G variant of amylin
    • Complex: two-protofilament amyloid fibrils of S20G variant of amylin
      • Protein or peptide: Islet amyloid polypeptide
Function / homology
Function and homology information


amylin receptor signaling pathway / Calcitonin-like ligand receptors / negative regulation of amyloid fibril formation / negative regulation of bone resorption / eating behavior / positive regulation of protein kinase A signaling / negative regulation of osteoclast differentiation / Regulation of gene expression in beta cells / negative regulation of protein-containing complex assembly / bone resorption ...amylin receptor signaling pathway / Calcitonin-like ligand receptors / negative regulation of amyloid fibril formation / negative regulation of bone resorption / eating behavior / positive regulation of protein kinase A signaling / negative regulation of osteoclast differentiation / Regulation of gene expression in beta cells / negative regulation of protein-containing complex assembly / bone resorption / sensory perception of pain / positive regulation of calcium-mediated signaling / osteoclast differentiation / hormone activity / cell-cell signaling / amyloid-beta binding / G alpha (s) signalling events / positive regulation of MAPK cascade / receptor ligand activity / positive regulation of apoptotic process / Amyloid fiber formation / signaling receptor binding / lipid binding / apoptotic process / signal transduction / extracellular space / extracellular region / identical protein binding
Similarity search - Function
Islet amyloid polypeptide / Calcitonin-like / Calcitonin peptide-like / Calcitonin, conserved site / Calcitonin / CGRP / IAPP family signature. / calcitonin / Calcitonin/adrenomedullin / Calcitonin / CGRP / IAPP family
Similarity search - Domain/homology
Islet amyloid polypeptide
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodhelical reconstruction / cryo EM / Resolution: 3.9 Å
AuthorsGallardo RU / Iadanza MG / Ranson NA / Radford SE
Funding support United Kingdom, 2 items
OrganizationGrant numberCountry
Wellcome TrustWT 204963 United Kingdom
Wellcome Trust108466/Z/15/Z United Kingdom
CitationJournal: Nat Struct Mol Biol / Year: 2020
Title: Fibril structures of diabetes-related amylin variants reveal a basis for surface-templated assembly.
Authors: Rodrigo Gallardo / Matthew G Iadanza / Yong Xu / George R Heath / Richard Foster / Sheena E Radford / Neil A Ranson /
Abstract: Aggregation of the peptide hormone amylin into amyloid deposits is a pathological hallmark of type-2 diabetes (T2D). While no causal link between T2D and amyloid has been established, the S20G ...Aggregation of the peptide hormone amylin into amyloid deposits is a pathological hallmark of type-2 diabetes (T2D). While no causal link between T2D and amyloid has been established, the S20G mutation in amylin is associated with early-onset T2D. Here we report cryo-EM structures of amyloid fibrils of wild-type human amylin and its S20G variant. The wild-type fibril structure, solved to 3.6-Å resolution, contains two protofilaments, each built from S-shaped subunits. S20G fibrils, by contrast, contain two major polymorphs. Their structures, solved at 3.9-Å and 4.0-Å resolution, respectively, share a common two-protofilament core that is distinct from the wild-type structure. Remarkably, one polymorph contains a third subunit with another, distinct, cross-β conformation. The presence of two different backbone conformations within the same fibril may explain the increased aggregation propensity of S20G, and illustrates a potential structural basis for surface-templated fibril assembly.
History
DepositionJul 14, 2020-
Header (metadata) releaseSep 30, 2020-
Map releaseSep 30, 2020-
UpdateNov 18, 2020-
Current statusNov 18, 2020Processing site: PDBe / Status: Released

-
Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.035
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by cylindrical radius
  • Surface level: 0.035
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: PDB-6zrq
  • Surface level: 0.035
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_11382.png

Downloads & links

-
Map

FileDownload / File: emd_11382.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.07 Å/pix.
x 300 pix.
= 319.5 Å		1.07 Å/pix.
x 300 pix.
= 319.5 Å		1.07 Å/pix.
x 300 pix.
= 319.5 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.065 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.035 / Movie #1: 0.035
Minimum - Maximum-0.03146062 - 0.07694056
Average (Standard dev.)0.0000646648 (±0.0012930926)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions300300300
Spacing300300300
CellA=B=C: 319.50003 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.0651.0651.065
M x/y/z300300300
origin x/y/z0.0000.0000.000
length x/y/z319.500319.500319.500
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS300300300
D min/max/mean-0.0310.0770.000

-
Supplemental data

-
Sample components

-
Entire : two-protofilament amyloid fibrils of S20G variant of amylin

EntireName: two-protofilament amyloid fibrils of S20G variant of amylin
Components
  • Complex: two-protofilament amyloid fibrils of S20G variant of amylin
    • Complex: two-protofilament amyloid fibrils of S20G variant of amylin
      • Protein or peptide: Islet amyloid polypeptide

-
Supramolecule #1: two-protofilament amyloid fibrils of S20G variant of amylin

SupramoleculeName: two-protofilament amyloid fibrils of S20G variant of amylin
type: complex / ID: 1 / Parent: 0 / Macromolecule list: all

-
Supramolecule #2: two-protofilament amyloid fibrils of S20G variant of amylin

SupramoleculeName: two-protofilament amyloid fibrils of S20G variant of amylin
type: complex / ID: 2 / Parent: 1 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: synthetic construct (others)

-
Macromolecule #1: Islet amyloid polypeptide

MacromoleculeName: Islet amyloid polypeptide / type: protein_or_peptide / ID: 1 / Details: TYC = C-terminal amidated Tyr / Number of copies: 12 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 3.878293 KDa
SequenceString:
KCNTATCATQ RLANFLVHSG NNFGAILSST NVGSNT(TYC)

-
Experimental details

-
Structure determination

Methodcryo EM
Processinghelical reconstruction
Aggregation statefilament

-
Sample preparation

Concentration0.12 mg/mL
BufferpH: 6.8 / Component - Concentration: 20.0 mM / Component - Formula: NH4CH3CO / Component - Name: ammonium acetate
GridModel: Homemade / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: PLASMA CLEANING
VitrificationCryogen name: ETHANE / Chamber humidity: 85 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV
DetailsSynthetically produced, oxidised and C-terminally amidated

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Specialist opticsEnergy filter - Name: GIF Quantum LS / Energy filter - Slit width: 20 eV
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average exposure time: 13.0 sec. / Average electron dose: 54.73 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal magnification: 130000
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

Final reconstructionNumber classes used: 1
Applied symmetry - Helical parameters - Δz: 2.41 Å
Applied symmetry - Helical parameters - Δ&Phi: 179.05 °
Applied symmetry - Helical parameters - Axial symmetry: C1 (asymmetric)
Resolution.type: BY AUTHOR / Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 3.0) / Number images used: 11901
CTF correctionSoftware - Name: Gctf (ver. 1.18)
Segment selectionNumber selected: 64274 / Software - Name: RELION (ver. 3.0)
Startup modelType of model: INSILICO MODEL
In silico model: model generated with relion v3.1 based on 2D class averages
Final angle assignmentType: NOT APPLICABLE
FSC plot (resolution estimation)

+
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