TY - JOUR
T1 - A p.Arg127Gln variant in GPIba LRR5 allosterically enhances affinity for VWF
T2 - a novel form of platelet-type VWD
AU - Bury, Loredana
AU - Falcinelli, Emanuela
AU - Bhotla, Haripriya Kuchi
AU - Mezzasoma, Anna Maria
AU - Guglielmini, Giuseppe
AU - Tischer, Alexander
AU - Moon-Tasson, Laurie
AU - Auton, Matthew
AU - Gresele, Paolo
N1 - Publisher Copyright:
© 2022 American Society of Hematology. All rights reserved.
PY - 2022/4/12
Y1 - 2022/4/12
N2 - having little effect on the dynamics of the LRR locally, enhances the conformational dynamics of the GPIba C-terminal disulfide loop structure. Our data demonstrate for the first time that GOF variants outside the GPIba C-terminal disulfide loop may be pathogenic and that aminoacidic changes in the LRR may cause allosterically conformational changes in the C-terminal disulfide loop of GPIba, inducing a conformation with high affinity for VWF.
AB - having little effect on the dynamics of the LRR locally, enhances the conformational dynamics of the GPIba C-terminal disulfide loop structure. Our data demonstrate for the first time that GOF variants outside the GPIba C-terminal disulfide loop may be pathogenic and that aminoacidic changes in the LRR may cause allosterically conformational changes in the C-terminal disulfide loop of GPIba, inducing a conformation with high affinity for VWF.
UR - http://www.scopus.com/inward/record.url?scp=85128273969&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85128273969&partnerID=8YFLogxK
U2 - 10.1182/bloodadvances.2021005463
DO - 10.1182/bloodadvances.2021005463
M3 - Article
C2 - 34619770
AN - SCOPUS:85128273969
SN - 2473-9529
VL - 6
SP - 2236
EP - 2246
JO - Blood Advances
JF - Blood Advances
IS - 7
ER -