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- EMDB-47715: Integrin aIIbb3 intermediate conformation from human platelet mem... -

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Basic information

Entry
Database: EMDB / ID: EMD-47715
TitleIntegrin aIIbb3 intermediate conformation from human platelet membrane crude preparation
Map data
Sample
  • Complex: Integrin aIIbb3
    • Protein or peptide: Integrin alpha-IIb
    • Protein or peptide: Integrin beta-3
  • Ligand: CALCIUM ION
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: MAGNESIUM ION
Keywordsplatelet membrane protein integrin aIIbb3 / BLOOD CLOTTING
Function / homology
Function and homology information


tube development / regulation of serotonin uptake / positive regulation of adenylate cyclase-inhibiting opioid receptor signaling pathway / alpha9-beta1 integrin-ADAM8 complex / regulation of trophoblast cell migration / integrin alphaIIb-beta3 complex / regulation of postsynaptic neurotransmitter receptor diffusion trapping / maintenance of postsynaptic specialization structure / alphav-beta3 integrin-vitronectin complex / regulation of extracellular matrix organization ...tube development / regulation of serotonin uptake / positive regulation of adenylate cyclase-inhibiting opioid receptor signaling pathway / alpha9-beta1 integrin-ADAM8 complex / regulation of trophoblast cell migration / integrin alphaIIb-beta3 complex / regulation of postsynaptic neurotransmitter receptor diffusion trapping / maintenance of postsynaptic specialization structure / alphav-beta3 integrin-vitronectin complex / regulation of extracellular matrix organization / positive regulation of glomerular mesangial cell proliferation / platelet alpha granule membrane / integrin alphav-beta3 complex / negative regulation of lipoprotein metabolic process / alphav-beta3 integrin-PKCalpha complex / fibrinogen binding / blood coagulation, fibrin clot formation / alphav-beta3 integrin-HMGB1 complex / vascular endothelial growth factor receptor 2 binding / negative regulation of lipid transport / positive regulation of vascular endothelial growth factor signaling pathway / regulation of release of sequestered calcium ion into cytosol / Elastic fibre formation / mesodermal cell differentiation / glycinergic synapse / cell-substrate junction assembly / alphav-beta3 integrin-IGF-1-IGF1R complex / platelet-derived growth factor receptor binding / positive regulation of bone resorption / filopodium membrane / extracellular matrix binding / negative regulation of low-density lipoprotein particle clearance / angiogenesis involved in wound healing / positive regulation of vascular endothelial growth factor receptor signaling pathway / apolipoprotein A-I-mediated signaling pathway / positive regulation of cell adhesion mediated by integrin / regulation of bone resorption / positive regulation of leukocyte migration / apoptotic cell clearance / wound healing, spreading of epidermal cells / positive regulation of fibroblast migration / integrin complex / heterotypic cell-cell adhesion / positive regulation of smooth muscle cell migration / smooth muscle cell migration / Molecules associated with elastic fibres / positive regulation of cell-matrix adhesion / negative chemotaxis / Mechanical load activates signaling by PIEZO1 and integrins in osteocytes / Syndecan interactions / cell adhesion mediated by integrin / p130Cas linkage to MAPK signaling for integrins / positive regulation of osteoblast proliferation / cellular response to insulin-like growth factor stimulus / protein disulfide isomerase activity / regulation of postsynaptic neurotransmitter receptor internalization / microvillus membrane / cell-substrate adhesion / platelet-derived growth factor receptor signaling pathway / PECAM1 interactions / GRB2:SOS provides linkage to MAPK signaling for Integrins / TGF-beta receptor signaling activates SMADs / fibronectin binding / lamellipodium membrane / negative regulation of macrophage derived foam cell differentiation / negative regulation of lipid storage / ECM proteoglycans / Integrin cell surface interactions / positive regulation of T cell migration / negative regulation of endothelial cell apoptotic process / coreceptor activity / cell adhesion molecule binding / cellular response to platelet-derived growth factor stimulus / positive regulation of endothelial cell proliferation / Integrin signaling / positive regulation of substrate adhesion-dependent cell spreading / embryo implantation / positive regulation of smooth muscle cell proliferation / positive regulation of endothelial cell migration / substrate adhesion-dependent cell spreading / protein kinase C binding / Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells / cell-matrix adhesion / Signal transduction by L1 / response to activity / integrin-mediated signaling pathway / regulation of actin cytoskeleton organization / wound healing / cellular response to mechanical stimulus / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / Signaling by high-kinase activity BRAF mutants / cell-cell adhesion / MAP2K and MAPK activation / platelet activation / platelet aggregation / VEGFA-VEGFR2 Pathway / ruffle membrane / integrin binding / cellular response to xenobiotic stimulus / positive regulation of fibroblast proliferation
Similarity search - Function
Integrin beta, epidermal growth factor-like domain 1 / Integrin beta epidermal growth factor like domain 1 / Integrin beta tail domain / Integrin beta subunit, cytoplasmic domain / Integrin beta cytoplasmic domain / Integrin_b_cyt / : / Integrin alpha Ig-like domain 3 / Integrin EGF domain / Integrin beta subunit, tail ...Integrin beta, epidermal growth factor-like domain 1 / Integrin beta epidermal growth factor like domain 1 / Integrin beta tail domain / Integrin beta subunit, cytoplasmic domain / Integrin beta cytoplasmic domain / Integrin_b_cyt / : / Integrin alpha Ig-like domain 3 / Integrin EGF domain / Integrin beta subunit, tail / Integrin beta tail domain superfamily / Integrin_B_tail / EGF-like domain, extracellular / EGF-like domain / Integrin alpha cytoplasmic region / Integrins beta chain EGF (I-EGF) domain profile. / Integrin beta subunit, VWA domain / Integrin beta subunit / Integrin beta N-terminal / Integrin beta chain VWA domain / Integrin plexin domain / Integrins beta chain EGF (I-EGF) domain signature. / Integrin beta subunits (N-terminal portion of extracellular region) / Integrin alpha-2 / Integrin alpha Ig-like domain 1 / Integrin alpha chain, C-terminal cytoplasmic region, conserved site / Integrins alpha chain signature. / Integrin alpha chain / Integrin alpha beta-propellor / : / Integrin alpha Ig-like domain 2 / FG-GAP repeat profile. / Integrin alpha (beta-propellor repeats). / FG-GAP repeat / FG-GAP repeat / Integrin alpha, N-terminal / Integrin domain superfamily / PSI domain / domain found in Plexins, Semaphorins and Integrins / von Willebrand factor A-like domain superfamily / EGF-like domain signature 1. / EGF-like domain signature 2.
Similarity search - Domain/homology
Integrin beta-3 / Integrin alpha-IIb
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.67 Å
AuthorsHan X / Nieman MT
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)HL098217 United States
CitationJournal: 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.
History
DepositionNov 5, 2024-
Header (metadata) releaseOct 15, 2025-
Map releaseOct 15, 2025-
UpdateOct 15, 2025-
Current statusOct 15, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_47715.png

Downloads & links

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Map

FileDownload / File: emd_47715.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

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AxesZ (Sec.)Y (Row.)X (Col.)
1.07 Å/pix.
x 300 pix.
= 321. Å		1.07 Å/pix.
x 300 pix.
= 321. Å		1.07 Å/pix.
x 300 pix.
= 321. Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.07 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.1
Minimum - Maximum-0.39849317 - 1.0587256
Average (Standard dev.)-0.0004218453 (±0.017270861)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions300300300
Spacing300300300
CellA=B=C: 321.00003 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_47715_half_map_1.map
Projections & Slices
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Half map: #1

Fileemd_47715_half_map_2.map
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Sample components

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Entire : Integrin aIIbb3

EntireName: Integrin aIIbb3
Components
  • Complex: Integrin aIIbb3
    • Protein or peptide: Integrin alpha-IIb
    • Protein or peptide: Integrin beta-3
  • Ligand: CALCIUM ION
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: MAGNESIUM ION

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Supramolecule #1: Integrin aIIbb3

SupramoleculeName: Integrin aIIbb3 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Integrin alpha-IIb

MacromoleculeName: Integrin alpha-IIb / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 65.023895 KDa
SequenceString: LNLDPVQLTF YAGPNGSQFG FSLDFHKDSH GRVAIVVGAP RTLGPSQEET GGVFLCPWRA EGGQCPSLLF DLRDETRNVG SQTLQTFKA RQGLGASVVS WSDVIVACAP WQHWNVLEKT EEAEKTPVGS CFLAQPESGR RAEYSPCRGN TLSRIYVEND F SWDKRYCE ...String:
LNLDPVQLTF YAGPNGSQFG FSLDFHKDSH GRVAIVVGAP RTLGPSQEET GGVFLCPWRA EGGQCPSLLF DLRDETRNVG SQTLQTFKA RQGLGASVVS WSDVIVACAP WQHWNVLEKT EEAEKTPVGS CFLAQPESGR RAEYSPCRGN TLSRIYVEND F SWDKRYCE AGFSSVVTQA GELVLGAPGG YYFLGLLAQA PVADIFSSYR PGILLWHVSS QSLSFDSSNP EYFDGYWGYS VA VGEFDGD LNTTEYVVGA PTWSWTLGAV EILDSYYQRL HRLRGEQMAS YFGHSVAVTD VNGDGRHDLL VGAPLYMESR ADR KLAEVG RVYLFLQPRG PHALGAPSLL LTGTQLYGRF GSAIAPLGDL DRDGYNDIAV AAPYGGPSGR GQVLVFLGQS EGLR SRPSQ VLDSPFPTGS AFGFSLRGAV DIDDNGYPDL IVGAYGANQV AVYRAQPVVK ASVQLLVQDS LNPAVKSCVL PQTKT PVSC FNIQMCVGAT GHNIPQKLSL NAELQLDRQK PRQGRRVLLL GSQQAGTTLN LDLGGKHSPI CHTTMAFLRD EADFRD KLS PIVLSLNVSL PPTEAGMAPA VVLHGDTHVQ EQTRIVL

UniProtKB: Integrin alpha-IIb

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Macromolecule #2: Integrin beta-3

MacromoleculeName: Integrin beta-3 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 55.880992 KDa
SequenceString: GPNICTTRGV SSCQQCLAVS PMCAWCSDEA LPLGSPRCDL KENLLKDNCA PESIEFPVSE ARVLEDRPLS DKGSGDSSQV TQVSPQRIA LRLRPDDSKN FSIQVRQVED YPVDIYYLMD LSYSMKDDLW SIQNLGTKLA TQMRKLTSNL RIGFGAFVDK P VSPYMYIS ...String:
GPNICTTRGV SSCQQCLAVS PMCAWCSDEA LPLGSPRCDL KENLLKDNCA PESIEFPVSE ARVLEDRPLS DKGSGDSSQV TQVSPQRIA LRLRPDDSKN FSIQVRQVED YPVDIYYLMD LSYSMKDDLW SIQNLGTKLA TQMRKLTSNL RIGFGAFVDK P VSPYMYIS PPEALENPCY DMKTTCLPMF GYKHVLTLTD QVTRFNEEVK KQSVSRNRDA PEGGFDAIMQ ATVCDEKIGW RN DASHLLV FTTDAKTHIA LDGRLAGIVQ PNDGQCHVGS DNHYSASTTM DYPSLGLMTE KLSQKNINLI FAVTENVVNL YQN YSELIP GTTVGVLSMD SSNVLQLIVD AYGKIRSKVE LEVRDLPEEL SLSFNATCLN NEVIPGLKSC MGLKIGDTVS FSIE AKVRG CPQEKEKSFT IKPVGFKDSL IVQVTFDCDC ACQAQAEPNS HRCNNGNGTF ECGVCRCGPG WLGSQCECSE EDYRP SQQD ECSPREGQPV CSQRGECLCG QC

UniProtKB: Integrin beta-3

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Macromolecule #5: CALCIUM ION

MacromoleculeName: CALCIUM ION / type: ligand / ID: 5 / Number of copies: 6 / Formula: CA
Molecular weightTheoretical: 40.078 Da

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Macromolecule #6: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 4 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

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Macromolecule #7: MAGNESIUM ION

MacromoleculeName: MAGNESIUM ION / type: ligand / ID: 7 / Number of copies: 1 / Formula: MG
Molecular weightTheoretical: 24.305 Da

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.4
VitrificationCryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 36.4 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: INSILICO MODEL
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.67 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 518071
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION
FSC plot (resolution estimation)

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