Wendy Stam: Revealing How Anti-HPA-1a Antibodies Lock Integrins in an Inactive State
Wendy Stam, PHD Candidate at Leiden University, shared a post on LinkedIn about a recent article she and her colleagues co-authored, published in Blood, adding:
“I am excited and grateful to share that not one, but two papers, showcasing my PhD work, were published recently!
We have shown that binding of anti-HPA-1a antibodies to both αvβ3 and αIIbβ3 integrins, inhibit integrin function by retaining the integrin in the bent conformation, impairing integrin activation and platelet aggregation. (Blood, PMID: 41980042)
On top of that, in close collaboration with Cryo-EM experts, we were able to visualize the binding of an anti-HPA-1a antibody in complex with the αIIbβ3 integrin, explaining this inactive integrin lock mechanism. (Science Advances, PMID: 42467762)
A big thank you to the people who participated and made this a success; Femke van der Meer, Jeremy Broekhuis, Janita Oosterhoff, Marcos Gragera Cabezudo, Gestur Vidarsson, Ellen van der Schoot, José de Pereda and Coert Margadant.”
Title: Maternal anti-HPA-1a antibodies block αIIbβ3/αvβ3 integrin activation, and blockade correlates with FNAIT disease severity
Authors: Wendy Stam, Jeremy D. Broekhuis, Femke W. T. van der Meer, Raoul P. Pirée, Janita J. Oosterhoff, José María de Pereda, Ellen van der Schoot, Gestur Vidarsson, Coert Margadant
Title: High-resolution cryo-EM structure of integrin αIIbβ3 bound to disease-causing maternal HPA-1a antibody that blocks integrin activation
Authors: José M. de Pereda, Wendy Stam, Marcos Gragera, Femke van der Meer, Francisco J. Chichón, Eleftherios Zarkadas, Ellen van der Schoot, Gestur Vidarsson, Junichi Takagi, Coert Margadant
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