Linker regions and flexibility around the metalloprotease domain account for conformational activation of ADAMTS-13.

ABSTRACT:

Background

Recently, conformational activation of ADAMTS-13 was identified. This mechanism showed the evolution from a condensed conformation, in which the proximal MDTCS and distal T2-CUB2 domains are in close contact with each other, to an activated, open structure due to binding with von Willebrand factor (VWF).

Objectives

Identification of cryptic epitope/exosite exposure after conformational activation and of sites of flexibility in ADAMTS-13.

Methods

The activating effect of 25 anti-T2-CUB2 antibodies was studied in the FRETS-VWF73 and the vortex assay. Cryptic epitope/exosite exposure was determined with ELISA and VWF binding assay. The molecular basis for flexibility was hypothesized through rapid automatic detection and alignment of repeats (RADAR) analysis,

SUBMITTER: Deforche L 

PROVIDER: S-EPMC4778570 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature