James T. B. Crawley
Imperial College London
Binding siteBiophysicsInternal medicineMolecular biologyReceptorChemistryImmunologyADAMTSThrombinVon Willebrand factorADAMTS13Protein CProteolysisActive siteProtein structureBiochemistryMedicineBiologyPlateletCell biologyVon Willebrand factor type A domain
74Publications
30H-index
2,932Citations
Publications 72
Newest
#1Adela Constantinescu-Bercu (Imperial College London)H-Index: 2
#2Yuxiao Alice Wang (Imperial College London)
Last. Isabelle I. Salles-Crawley (Imperial College London)H-Index: 6
view all 7 authors...
The GPIbT-VWF A1 domain interaction is essential for platelet tethering under high shear. Synergy between GPIbα and GPVI signaling machineries has been suggested previously, however its molecular mechanism remains unclear. We generated a novel GPIbα transgenic mouse (GpIbαΔsig/Δsig) by CRISPR-Cas9 technology to delete the last 24 residues of the GPIbα intracellular tail that harbors the 14-3-3 and phosphoinositide-3 kinase binding sites. GPIbαΔsig/Δsig platelets bound VWF normally under flow. Ho...
Source
#1Hyo Jung Kim (University of Nottingham)H-Index: 2
#2Y. Xu (Imperial College London)
Last. Jonas Emsley (University of Nottingham)H-Index: 37
view all 6 authors...
ADAMTS13 is a plasma metalloprotease that is essential for the regulation of von Willebrand factor (VWF) function, mediator of platelet recruitment to sites of blood vessel damage. ADAMTS13 function is dynamically regulated by structural changes induced by VWF binding that convert it from a latent to active conformation. ADAMTS13 global latency is manifest by the interaction of its C-terminal CUB1-2 domains with its central Spacer domain. We resolved the crystal structure of the ADAMTS13 CUB1-2 ...
Source
#1Plinio Ferreira (University of Reading)H-Index: 3
#2E Bozbas (University of Reading)H-Index: 1
Last. Parveen Yaqoob (University of Reading)H-Index: 68
view all 10 authors...
Platelet-derived extracellular vesicles (PDEVs) are the most abundant amongst all types of EVs in the circulation. However, the mechanisms leading to PDEVs release, their role in coagulation and phenotypic composition are poorly understood. PDEVs from washed platelets were generated using different stimuli and were characterised using nanoparticle tracking analysis. Procoagulant properties were evaluated by fluorescence flow cytometry and calibrated automated thrombography. EVs from plasma were ...
1 CitationsSource
#1Adela Constantinescu-Bercu (Imperial College London)H-Index: 2
#2Isabelle I. Salles-Crawley (Imperial College London)H-Index: 6
Last. James T. B. Crawley (Imperial College London)H-Index: 30
view all 3 authors...
3 CitationsSource
#1Adela Constantinescu-Bercu (Imperial College London)H-Index: 2
#2Luigi Grassi (University of Cambridge)H-Index: 60
Last. James T. B. Crawley (Imperial College London)H-Index: 30
view all 6 authors...
Platelet-neutrophil interactions are important for innate immunity, but also contribute to the pathogenesis of deep vein thrombosis, myocardial infarction and stroke. Here we report that, under flow, von Willebrand factor/glycoprotein Iba-dependent platelet 'priming' induces integrin aIIbb3 activation that, in turn, mediates neutrophil and T-cell binding. Binding of platelet aIIbb3 to SLC44A2 on neutrophils leads to mechanosensitive-dependent production of highly prothrombotic neutrophil extrace...
22 CitationsSource
#1An-Sofie Schelpe (Katholieke Universiteit Leuven)H-Index: 6
#2Anastasis Petri (Imperial College London)H-Index: 2
Last. Karen Vanhoorelbeke (Katholieke Universiteit Leuven)H-Index: 45
view all 8 authors...
Plasma ADAMTS13 circulates in a folded conformation that is stabilized by an interaction between the central Spacer domain and the C-terminal CUB (complement components C1r and C1s, sea urchin protein Uegf, and bone morphogenetic protein-1) domains. Binding of ADAMTS13 to the VWF D4(-CK) domains or to certain activating murine monoclonal antibodies (mAbs) induces a structural change that extends ADAMTS13 into an open conformation that enhances its function. The objective was to characterize the ...
11 CitationsSource
#1Adela Constantinescu-Bercu (Imperial College London)H-Index: 2
#2Luigi Grassi (University of Cambridge)H-Index: 60
Last. James T. B. Crawley (Imperial College London)H-Index: 30
view all 6 authors...
Source
#1Anastasis Petri (Imperial College London)H-Index: 2
#2Hyo Jung Kim (University of Nottingham)H-Index: 2
Last. James T. B. Crawley (Imperial College London)H-Index: 30
view all 9 authors...
Platelet recruitment to sites of blood vessel damage is highly dependent upon von Willebrand factor (VWF). VWF platelet-tethering function is proteolytically regulated by the metalloprotease ADAMTS13. Proteolysis depends upon shear-induced conformational changes in VWF that reveal the A2 domain cleavage site. Multiple ADAMTS13 exosite interactions are involved in recognition of the unfolded A2 domain. Here we report through kinetic analyses that, in binding VWF, the ADAMTS13 cysteine-rich and sp...
20 CitationsSource
#1Magdalena Gierula (Imperial College London)H-Index: 8
#2Isabelle I. Salles-Crawley (Imperial College London)H-Index: 6
Last. Josefin Ahnström (Imperial College London)H-Index: 16
view all 7 authors...
BACKGROUND: Activated protein C (APC)-mediated inactivation of factor (F)Va is greatly enhanced by protein S. For inactivation to occur, a trimolecular complex among FVa, APC, and protein S must form on the phospholipid membrane. However, direct demonstration of complex formation has proven elusive. OBJECTIVES: To elucidate the nature of the phospholipid-dependent interactions among APC, protein S, and FVa. METHODS: We evaluated binding of active site blocked APC to phospholipid-coated magnetic ...
5 CitationsSource
#1James T. B. Crawley (Hammersmith Hospital)H-Index: 30
#1James T. B. Crawley (Hammersmith Hospital)
Last. Isabelle I. Salles‐Crawley (Hammersmith Hospital)
view all 7 authors...
BACKGROUND: Bone morphogenetic and activin membrane-bound inhibitor (BAMBI) is a transmembrane protein related to the type I transforming growth factor- β (TGF-β) receptor family that is present on both platelets and endothelial cells (ECs). Bambi-deficient mice exhibit reduced hemostatic function and thrombus stability characterized by an increased embolization. OBJECTIVE: We aimed to delineate how BAMBI influences endothelial function and thrombus stability. METHODS: Bambi-deficient mice were ...
2 CitationsSource