Proteolysis of human. cap alpha. /sub 2/-macroglobulin without hydrolysis of the internal thiolesters or expression of the receptor recognition site

Journal Article · Mon Jan 04 23:00:00 EST 1988 · J. Biol. Chem.; (United States)

OSTI ID:6924778

Leuven, F V; Marynen, P; Cassiman, J J; Berghe, H V.D.

Proteolysis of human ..cap alpha../sub 2/-macroglobulin (..cap alpha../sub 2/M) in the bait region is the prerequisite and necessary trigger for the trapping of the proteinase by a massive conformational change of ..cap alpha../sub 2/M. This labilization of the native conformation of ..cap alpha../sub 2/M is mediated by activation of the internal thiolesters, but the underlying mechanism is unknown. The authors now describe observations on proteolysis of human ..cap alpha../sub 2/M without concomitant hydrolysis of the internal thiolesters or conformational change. This proteolysis was obtained with a novel bacterial proteinase they recently used to isolate the receptor-binding domain from ..cap alpha../sub 2/M. This proteinase is not inhibited by ..cap alpha../sub 2/M, and therefore it was possible to study its effect on native ..cap alpha../sub 2/M at pH 4.5, conditions used previously to produce the receptor-binding domain. The major observations are that despite extensive proteolysis, ..cap alpha../sub 2/M largely retained its native conformation as shown by rate electrophoresis, the absence of binding of monoclonal antibody F2B2, and the incorporation of (/sup 14/C)methylamine into a 145-kDa fragment of ..cap alpha../sub 2/M. These results demonstrate indirectly the particular relation of the bait region to the internal thiolesters and illustrate further the domain-structure of ..cap alpha../sub 2/M and the expression of the receptor-recognition site by activation of the internal thiolesters.

• Research Organization: Univ. of Leuven (Belgium)
• OSTI ID: 6924778
• Journal Information: J. Biol. Chem.; (United States), Journal Name: J. Biol. Chem.; (United States) Vol. 263:1; ISSN JBCHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANIMALS
ANTIBODIES
BIOCHEMISTRY
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CHEMICAL REACTIONS
CHEMISTRY
CONFORMATIONAL CHANGES
DECOMPOSITION
ELECTROPHORESIS
ENZYMES
GLOBULINS
GLOBULINS-ALPHA
HYDROLASES
LABELLED COMPOUNDS
LYSINE
MAMMALS
MAN
MEMBRANE PROTEINS
MONOCLONAL ANTIBODIES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PEPTIDE HYDROLASES
PRIMATES
PROTEINS
PROTEOLYSIS
RECEPTORS
THIOLS
VERTEBRATES