STRUCTURE/FUNCTION OF BLOOD PLATELET GPIIB-IIIA

Project: Research project

Project Details

Description

DESCRIPTION: (Adapted from Applicant's Abstract) The overall objective of
this work is to produce a molecular map of the structural basis for platelet
interaction (specifically GBIIb-IIIa) with adhesive proteins. The
hypothesis states that multiple ligand contact points govern high affinity
binding between IIb-IIIa and its various adhesive protein ligands, and the
overall goal of the current work is to identify individual amino acids in
each receptor subunit that are essential for ligand binding. The first
Specific Aim is to generate an "entire" library of potential mutations that
may play a role in ligand binding through the use of a random mutagenesis
approach. A screening methodology will be employed to enrich for mutants
that result in a loss of ligand binding. The second Aim is based on the
hypothesis that ligand recognition specificity is regulated by distinct
regions of IIb. The regions will be identified by the development and
assessment of chimeric alpha subunits that include different combination of
alpha subunit from IIb-IIIa and the vitronectin receptor. Major concerns
from last review were about interpreting data from loss-of-function
mutation, and the need to establish feasibility of methods that had been
proposed.
StatusNot started

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