Characterization of interaction between blood coagulation factor VIII and LRP1 suggests dynamic binding by alternating complex contacts.

ABSTRACT:

Background

Deficiency in blood coagulation factor VIII (FVIII) results in life-threating bleeding (hemophilia A) treated by infusions of FVIII concentrates. To improve disease treatment, FVIII has been modified to increase its plasma half-life, which requires understanding mechanisms of FVIII catabolism. An important catabolic actor is hepatic low density lipoprotein receptor-related protein 1 (LRP1), which also regulates many other clinically significant processes. Previous studies showed complexity of FVIII site for binding LRP1.

Objectives

To characterize binding sites between FVIII and LRP1 and suggest a model of the interaction.

Methods

A series of recombinant ligand-binding complement-type repeat (CR) fragments of LRP1 including mutated variants was generated in

SUBMITTER: Chun H 

PROVIDER: S-EPMC9804390 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature