|Entry||Database: PDB / ID: 7m62|
|Title||Cryo-EM structure of human islet amyloid polypeptide (hIAPP, or amylin) fibrils seeded by patient extracted fibrils, polymorph 2|
|Components||Islet amyloid polypeptideAmylin|
|Keywords||PROTEIN FIBRIL / hIAPP / type II diabetes / amyloid|
|Function / homology|
Function and homology information
positive regulation of calcium ion import across plasma membrane / Calcitonin-like ligand receptors / amylin receptor signaling pathway / eating behavior / negative regulation of amyloid fibril formation / negative regulation of mitochondrion organization / negative regulation of bone resorption / positive regulation of protein kinase A signaling / Regulation of gene expression in beta cells / negative regulation of protein-containing complex assembly ...positive regulation of calcium ion import across plasma membrane / Calcitonin-like ligand receptors / amylin receptor signaling pathway / eating behavior / negative regulation of amyloid fibril formation / negative regulation of mitochondrion organization / negative regulation of bone resorption / positive regulation of protein kinase A signaling / Regulation of gene expression in beta cells / negative regulation of protein-containing complex assembly / negative regulation of cell differentiation / inclusion body / ADORA2B mediated anti-inflammatory cytokines production / adenylate cyclase-activating G protein-coupled receptor signaling pathway / positive regulation of cell death / sensory perception of pain / protein destabilization / G alpha (s) signalling events / protein homooligomerization / hormone activity / negative regulation of inflammatory response to antigenic stimulus / cell-cell signaling / amyloid-beta binding / positive regulation of cytosolic calcium ion concentration / positive regulation of MAPK cascade / positive regulation of peptidyl-serine phosphorylation / amyloid fibril formation / positive regulation of ERK1 and ERK2 cascade / positive regulation of protein kinase B signaling / G protein-coupled receptor signaling pathway / Amyloid fiber formation / negative regulation of cell population proliferation / positive regulation of apoptotic process / signaling receptor binding / neuronal cell body / apoptotic process / positive regulation of gene expression / signal transduction / extracellular space / extracellular region / identical protein binding
Similarity search - Function
Islet amyloid polypeptide / Calcitonin / CGRP / IAPP family signature. / calcitonin / Calcitonin, conserved site / Calcitonin peptide-like / Calcitonin-like / Calcitonin/adrenomedullin / Calcitonin / CGRP / IAPP family
Similarity search - Domain/homology
Islet amyloid polypeptide
Similarity search - Component
|Biological species||Homo sapiens (human)|
|Method||ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 3.9 Å|
|Authors||Cao, Q. / Boyer, D.R. / Sawaya, M.R. / Eisenberg, D.S.|
|Funding support|| United States, 1items |
|Citation||Journal: Nat Struct Mol Biol / Year: 2021|
Title: Cryo-EM structures of hIAPP fibrils seeded by patient-extracted fibrils reveal new polymorphs and conserved fibril cores.
Authors: Qin Cao / David R Boyer / Michael R Sawaya / Romany Abskharon / Lorena Saelices / Binh A Nguyen / Jiahui Lu / Kevin A Murray / Fouad Kandeel / David S Eisenberg /
Abstract: Amyloidosis of human islet amyloid polypeptide (hIAPP) is a pathological hallmark of type II diabetes (T2D), an epidemic afflicting nearly 10% of the world's population. To visualize disease-relevant ...Amyloidosis of human islet amyloid polypeptide (hIAPP) is a pathological hallmark of type II diabetes (T2D), an epidemic afflicting nearly 10% of the world's population. To visualize disease-relevant hIAPP fibrils, we extracted amyloid fibrils from islet cells of a T2D donor and amplified their quantity by seeding synthetic hIAPP. Cryo-EM studies revealed four fibril polymorphic atomic structures. Their resemblance to four unseeded hIAPP fibrils varies from nearly identical (TW3) to non-existent (TW2). The diverse repertoire of hIAPP polymorphs appears to arise from three distinct protofilament cores entwined in different combinations. The structural distinctiveness of TW1, TW2 and TW4 suggests they may be faithful replications of the pathogenic seeds. If so, the structures determined here provide the most direct view yet of hIAPP amyloid fibrils formed during T2D.
|Structure viewer||Molecule: |
Downloads & links
A: Islet amyloid polypeptide
B: Islet amyloid polypeptide
C: Islet amyloid polypeptide
D: Islet amyloid polypeptide
E: Islet amyloid polypeptide
F: Islet amyloid polypeptide
G: Islet amyloid polypeptide
H: Islet amyloid polypeptide
I: Islet amyloid polypeptide
J: Islet amyloid polypeptide
|Symmetry||Helical symmetry: (Circular symmetry: 2 / Dyad axis: no / N subunits divisor: 1 / Num. of operations: 10 / Rise per n subunits: 4.8 Å / Rotation per n subunits: 178.42 °)|
Mass: 3907.312 Da / Num. of mol.: 10 / Fragment: C-terminal amidated peptide (UNP residues 34-70) / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: P10997
|Experiment||Method: ELECTRON MICROSCOPY|
|EM experiment||Aggregation state: FILAMENT / 3D reconstruction method: helical reconstruction|
|Component||Name: hIAPP fibril / Type: COMPLEX|
Details: Synthetic hIAPP seeded by hIAPP fibrils extracted from a patient with Type II Diabetes
Entity ID: #1 / Source: NATURAL
|Molecular weight||Units: KILODALTONS/NANOMETER / Experimental value: NO|
|Source (natural)||Organism: Homo sapiens (human)|
|Buffer solution||pH: 7.4 / Details: PBS buffer|
|Specimen||Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES|
|Specimen support||Grid material: COPPER / Grid type: Quantifoil R1.2/1.3|
|Vitrification||Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 298 K|
-Electron microscopy imaging
Model: Titan Krios / Image courtesy: FEI Company
|Microscopy||Model: FEI TITAN KRIOS|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM|
|Electron lens||Mode: BRIGHT FIELDBright-field microscopy|
|Image recording||Electron dose: 45 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 3|
|CTF correction||Type: PHASE FLIPPING AND AMPLITUDE CORRECTION|
|Helical symmerty||Angular rotation/subunit: 178.42 ° / Axial rise/subunit: 4.8 Å / Axial symmetry: C2|
|3D reconstruction||Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 23957 / Symmetry type: HELICAL|
|Atomic model building||B value: 98 / Protocol: AB INITIO MODEL / Space: REAL|
-Aug 12, 2020. Covid-19 info
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
- International Committee on Taxonomy of Viruses (ICTV) defined the short name of the 2019 coronavirus as "SARS-CoV-2".
- The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2 - nature microbiology
- In the structure databanks used in Yorodumi, some data are registered as the other names, "COVID-19 virus" and "2019-nCoV". Here are the details of the virus and the list of structure data.
Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info
+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
+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.
+Jun 16, 2017. Omokage search with filter
Omokage search with filter
Result of Omokage search can be filtered by keywords and the database types
Related info.:Omokage search
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