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 - Funding Information:
This work was supported by a Telethon grant (GGP15063) to P.G. and by a fellowship from Fondazione Umberto Veronesi to L.B. and E.F. and by the National Institutes of Health, Heart, Lung and Blood Institute (HL146508) to M.A. The authors thank A. Savoia (IRCCS “Burlo Garofolo,” Trieste, Italy) and Francois Lanza (UMR S_949 - EFS-Alsace, Strasbourg, France) for providing the CHO b/IX cells, Luigi De Marco (Department of Translational Research, National Cancer Center, Aviano, Italy) for providing the LJ-P19 antibody and human purified VWF, and Jose Rivera (University of Murcia, Murcia, Spain) for performing high-throughput-sequencing on patient DNA.
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 -