Three noncontiguous peptides comprise binding sites on high-molecular-weight kininogen to neutrophils.
The binding of high-molecular-weight kininogen (HK) to neutrophils (polymorphonuclear leukocytes, PMN) is required for the stimulation of aggregation and degranulation by human plasma kallikrein as well as the displacement of fibrinogen from this cell surface. The putative receptor for HK is the leukocyte integrin alphaMbeta2, and domains 3 (D3) and 5 (D5) of HK form its binding site. To further map the binding sites on HK for PMN, we used D3 recombinant exon products and designed peptides from D3 and D5. In D3, a heptapeptide, Leu271-Ala277, from exon 7 product, and a peptide, Cys333-Cys352, from exon 9 product can inhibit binding of kininogen to PMN. Two contiguous peptides from D5 in the histidine-glycine-rich region, Gly442-Lys458 and Phe459-Lys478, each inhibit the binding of HK to PMN. This study has thus delineated three noncontiguous surface-oriented sequences on HK, which together comprise all or most of the binding site for human PMN.
The Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
M M
MM
Khan
S P
SP
Kunapuli
Y
Y
Lin
A
A
Majluf-Cruz
R A
RA
Cadena
S L
SL
Cooper
R W
RW
Colman
D000595:Amino Acid Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D005091:Exons; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D019679:Kininogen, High-Molecular-Weight / Q000096:biosynthesis / Q000097:blood* / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000502:physiology*; D010446:Peptide Fragments / Q000097:blood / Q000737:chemistry; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000097:blood / Q000737:chemistry
D019679:Kininogen, High-Molecular-Weight; D010446:Peptide Fragments; D011994:Recombinant Proteins