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Title: Isolation and characterization of cDNAs encoding the heavy chain of human inter-. cap alpha. -trypsin inhibitor (I. cap alpha. TI): unambiguous evidence for multipolypeptide chain structure of I. cap alpha. TI

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)

Human inter-..cap alpha..-trypsin inhibitor (I..cap alpha..TI) is a plasma glycoprotein of M/sub r/ 180,000, which has been described as a single polypeptide chain. Recently, however, the authors proposed that I..cap alpha..TI might be composed of a heavy (H) chain (M/sub r/ = 95,000) and a light (L) chain (M/sub r/ = 40,000) synthesized by two separate mRNAs. In the present study they have characterized cDNAs for the H chain of I..cap alpha..TI. These cDNAs collectively covered two sequences (977 and 1450 base pairs in length) with single open reading frames. The deduced amino acid sequences were highly homologous to each other and well matched with partial amino acid sequences obtained from purified serum I..cap alpha..TI. RNA blot analyses of liver RNAs with H- or L-chain cDNAs as probes clearly identified two distinct mRNAs of 3.3 and 1.3 kilobases, which correspond to H or L chain, respectively. Poly(A)/sup +/ RNAs hybrid-selected with H-chain cDNAs coded for polypeptide chains of M/sub r/ 90,000-95,000. These results unambiguously establish that I..cap alpha..TI is made of multipolypeptides, possibly including one H and two L chains. The H chain contains potential calcium-binding sites and also regions homologous to the proposed reactive site for thiolproteinase inhibitors. These data indicate that I..cap alpha..TI is a complex, multifunctional protein. mRNAs for both the H and L chains were found only in liver.

Research Organization:
Institut National de la Sante et de la Recherche Medicale, Saint-Etienne-du-Rouvray (France)
OSTI ID:
6408987
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 84:23
Country of Publication:
United States
Language:
English