Hydrogen-deuterium exchange mass spectrometry highlights conformational changes induced by factor XI activation and binding of factor IX to factor XIa.

ABSTRACT:

Background

Factor XI (FXI) is a zymogen in the coagulation pathway that, once activated, promotes haemostasis by activating factor IX (FIX). Substitution studies using apple domains of the homologous protein prekallikrein have identified that FIX binds to the apple 3 domain of FXI. However, the molecular changes upon activation of FXI or binding of FIX to FXIa have remained largely unresolved.

Objectives

This study aimed to gain more insight in the FXI activation mechanism by identifying the molecular differences between FXI and FXIa, and in the conformational changes in FXIa induced by binding of FIX.

Methods

Hydrogen-deuterium exchange mass spectrometry was performed on FXI, FXIa, and FXIa in complex with FIX.

Results

Both activation and binding to FIX induce

SUBMITTER: Bar Barroeta A 

PROVIDER: S-EPMC6916417 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature