Mapping the interaction of bradykinin 1-5 with the exodomain of human protease activated receptor 4.
The angiotensin converting enzyme breakdown product of bradykinin, bradykinin 1-5 (RPPGF), inhibits thrombin-induced human or mouse platelet aggregation. RPPGF binds to the exodomain of human protease-activated receptor 1 (PAR1). Studies determined if RPPGF also binds to the exodomain of human PAR4. RPPGF binds to a peptide of the thrombin cleavage site on PAR4. Recombinant wild-type and mutated exodomain of human PAR4 was prepared. The N-terminal arginine on RPPGF binds to the P2 position or proline46 on PAR4 to block thrombin cleavage. These data indicate that RPPGF influences thrombin activity by binding to the thrombin cleavage site on both PAR4 and PAR1.
Nieman
Marvin T
MT
Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-0640, USA.
Pagan-Ramos
Eileen
E
Warnock
Mark
M
Krijanovski
Yelena
Y
Hasan
Ahmed A K
AA
Schmaier
Alvin H
AH
D001667:Binding, Competitive; D001710:Biotin / Q000737:chemistry; D001920:Bradykinin / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary / Q000235:genetics; D018179:Receptors, Thrombin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013917:Thrombin / Q000037:antagonists & inhibitors
D010446:Peptide Fragments; D018179:Receptors, Thrombin; D011994:Recombinant Proteins; C079000:bradykinin (1-5); D001710:Biotin; D013917:Thrombin; C112908:protease-activated receptor 4; D001920:Bradykinin