Structure-function correlates of human high molecular weight kininogen.
1. The first documented mutation responsible for total human kininogen deficiency has been characterized as a single base change from CGA to TGA in exon 5, resulting in an Arg-->Stop mutation inherited as an autosomal recessive trait. 2. The surface binding domain (D5) of high molecular weight kininogen (HK) was mapped by deletion mutagenesis into two regions, the first rich in histidine and glycine, and the second in histidine, glycine and lysine. 3. The structural requirements of domain 2 to inhibit calpain have been mapped using affinity labels and conformationally constrained peptides. The surface loops consist of a binding region QVVAG and an inhibitory region C-terminal consisting of a sequence containing the sequence NAYI. 4. Domain 3 contains structural components capable of inhibiting the binding of thrombin to platelets. 5. Each domain of HK has a unique function which contributes to different aspects of the inflammatory reactions mediated by plasma protein and blood cells.
Colman
R W
RW
Department of Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA.
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D006801:Humans; D007704:Kininogens / Q000737:chemistry / Q000502:physiology*; D008956:Models, Chemical; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011487:Protein Conformation; D051381:Rats; D011914:Rats, Inbred BN; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D007704:Kininogens