Soluble phosphatidylserine binds to a single identified site in the C2 domain of human factor Va.

Abstract:

:Factor V(a) (FV(a)) is a cofactor for the serine protease factor X(a) that activates prothrombin to thrombin in the presence of Ca(2+) and a membrane surface. FV(a) is a heterodimer composed of one heavy chain (A1 and A2 domains) and one light chain (A3, C1, and C2 domains). We use fluorescence, circular dichroism, and equilibrium dialysis to demonstrate that (1) the FV C2 domain expressed in Sf9 cells binds one molecule of C6PS with a k(d) of approximately 2 microM, (2) stabilizing changes occur in the FV C2 domain upon C6PS binding, (3) the C6PS binding site in the FV C2 domain is located near residue Cys(2113), which reacts with DTNB, and (4) binding to a PS-containing membrane is an order of magnitude tighter than that to soluble C6PS. Coupled with a recently published crystal structure of the C2 domain, these results support a model for the mechanism of C2-membrane interaction.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Srivastava A,Quinn-Allen MA,Kim SW,Kane WH,Lentz BR

doi

10.1021/bi010449k

subject

Has Abstract

pub_date

2001-07-27 00:00:00

pages

8246-55

issue

28

eissn

0006-2960

issn

1520-4995

pii

bi010449k

journal_volume

40

pub_type

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