Apolipoprotein E isoprotein-specific interactions with tissue plasminogen activator.
Apolipoprotein E (Apo E) is an important genetic risk factor for multiple neurological, vascular and cardiovascular diseases. Previously, we reported Apo E isoprotein-specific modulation of tissue plasminogen activator (tPA) using an in vitro blood-clotting assay. Here, we studied the conformational changes of Apo E2, E3 and E4 in the presence of tPA and vice versa using circular dichroism (CD) and dual polarization interferometry (DPI). We report isoprotein and state-specific intermolecular interactions between the Apo E isoforms and tPA. Apo E2 interaction with immobilized tPA leads to significant conformational changes which are not observed with Apo E3 or E4. Additionally, tPA induces changes in helicity of lipidated Apo E2 whereas no detectable changes were observed in Apo E3 or E4. The Tukey's test for interaction indicated a significant (P < 0.001) interaction between tPA and Apo E2 in the lipidated environment. These results may be important regarding the mechanism by which Apo E has isoprotein-specific effects on many biological processes and diseases involving blood clotting, proteolysis and perfusion.
Biehle
Susan J
SJ
Department of Neurology, University of Cincinnati Medical Center, ML 0536, OH 45267-0536, USA. Susan.Biehle@uc.edu
Carrozzella
Janice
J
Shukla
Rakesh
R
Popplewell
Jonathan
J
Swann
Marcus
M
Freeman
Neville
N
Clark
Joseph F
JF
D001057:Apolipoproteins E / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D001057:Apolipoproteins E; D010959:Tissue Plasminogen Activator