National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)
HL098217
United States
Citation
Journal: Blood Adv / Year: 2025 Title: Elucidating the dynamics of integrin αIIbβ3 from native platelet membranes by cryo-EM with build-and-retrieve method. Authors: Xu Han / Zhemin Zhang / Chih-Chia Su / Meinan Lyu / Masaru Miyagi / Edward Yu / Marvin T Nieman Abstract: Platelets fulfill their essential physiological roles sensing the extracellular environment through their membrane proteins. The native membrane environment provides essential regulatory cues that ...Platelets fulfill their essential physiological roles sensing the extracellular environment through their membrane proteins. The native membrane environment provides essential regulatory cues that affect the protein structure and mechanism of action. Single-particle cryogenic electron microscopy (cryo-EM) has transformed structural biology by allowing high-resolution structures of membrane proteins to be solved from homogeneous samples. Our recent breakthroughs in data processing now make it feasible to obtain atomic-level-resolution protein structures from crude preparations in their native environments by integrating cryo-EM with the "build-and-retrieve" (BaR) data processing methodology. We applied this iterative bottom-up methodology on resting human platelet membranes for an in-depth systems biology approach to uncover how lipids, metal binding, post-translational modifications, and cofactor associations in the native environment regulate platelet function at the molecular level. Here, we report using cryo-EM followed by the BaR method to solve the unmodified integrin αIIbβ3 structure directly from resting human platelet membranes in its inactivated and intermediate states at 2.75 and 2.67 Å, respectively. Furthermore, we also solved a novel dimer conformation of αIIbβ3 at 2.85 Å formed by 2 intermediate states of αIIbβ3. This may indicate a previously unknown self-regulatory mechanism of αIIbβ3 in its native environment. In conclusion, our data show the power of using cryo-EM with the BaR method to determine 3 distinct structures including a novel dimer directly from natural sources. This approach allows us to identify unrecognized regulation mechanisms for proteins without artifacts owing to purification processes. These data have the potential to enrich our understanding of platelet signaling circuitry.
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.
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
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
Movie
Controller
Yorodumi
Open data
Basic information
Map data
Sample
Keywords
Function and homology information
Homo sapiens (human)
Authors
United States, 1 items 
Citation
Structure visualization
Downloads & links
emd_47713.png
http://ftp.pdbj.org/pub/emdb/structures/EMD-47713
Z (Sec.)
Y (Row.)
X (Col.)
Sample components
Processing
Electron microscopy
FIELD EMISSION GUN
