Human α2-macroglobulin : time dependent degradation under denaturing conditions

Frénoy, Jean-Pierre; Bourrillon, R

doi:10.1016/s0300-9084(80)80069-1

Cited by 3 publications

(2 citation statements)

References 29 publications

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“…Of the multiple fragments produced for h-cX2M, only the 125000-Mr and 62000-Mr fragments are thought to result directly from the methylamine-sensitive site. Harpel et al (1979) did not address a mechanism for the generation of these additional fragments; however, Frenoy & Bourrillon (1980) have suggested that the additional fragments produced are the result of trapped proteinases that are active under conditions similar to the ones used in our study. Under identical conditions, M-AMG is also found to be thermally fragmented into multiple fragments, with the two major fragments having Mr 125000 and 29000.…”

Section: Discussionmentioning

confidence: 72%

“…Surprisingly, the 125 000-Mr fragment contained the tryptic peptides found in the 62000-Mr fragment (results not shown). Thus the M-AMG 62000-Mr fragment must have been generated from the 125 000-Mr fragment, possibly by the mechanism suggested by Frenoy & Bourrillon (1980). Since the 185 OOOMr polypeptide represents 6-10 % of the total M-AMG and is related to the 163000-Mr polypeptide, it was expected that a fragment somewhat larger or smaller than Mr 62000 might have been generated from the 185000-Mr polypeptide.…”

Section: Discussionmentioning

confidence: 99%

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Mouse α-macroglobulin. Structure, function and a molecular model

Hudson

Kehoe

Koo

1987

Biochemical Journal

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Mouse alpha-macroglobulin (M-AMG) is believed to be a functional homologue of human alpha 2-macroglobulin (h-alpha 2M). The subunit composition, the tryptic cleavage pattern before and after methylamine incorporation and the two-dimensional tryptic-peptide mapping, however, indicate that these two proteins are structurally distinct. M-AMG is composed of two major types of polypeptides (Mr 163,000 and 35,000) together with a minor polypeptide (Mr 185,000), whereas h-alpha 2M has only one type of polypeptide (Mr 185,000). After incorporation of methylamine, there is no change in the normal tryptic-cleavage pattern of M-AMG; however, tryptic cleavage of h-alpha 2M is severely retarded [Hudson & Koo (1982) Biochim. Biophys. Acta 704, 290-303]. The N-terminal sequence of the 163,000-Mr polypeptide of M-AMG shows sequence homology with the N-terminal sequence of h-alpha 2M. The amino acid compositions of M-AMG and its two major polypeptide chains are compared. Thermal fragmentation studies show that the 163,000-Mr polypeptide is broken down into 125,000-Mr and 29,000-Mr fragments. Trypsin-binding studies show that M-AMG can bind two molecules of trypsin/molecule. Inactivations of the trypsin-binding property of M-AMG and h-alpha 2M with methylamine show similar kinetics of inhibition at 4 degrees C. A structural model of M-AMG is proposed, based on accumulated data.

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Mouse α-macroglobulin. Structure, function and a molecular model

Hudson

Kehoe

Koo

1987

Biochemical Journal

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Isolation and characterization of horse α2-macroglobulin protease inhibitor

Pellegrini

Zweifel

Fellenberg

1983

International Journal of Biochemistry

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Autolytic Fragmentation of Complement Components C3 and C4 and Its Relationship to Covalent Binding Activity

Sim

1983

Annals of the New York Academy of Sciences

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The autolytic cleavage reaction of C3 and C4 and the covalent binding reaction of these proteins, are both aspects of the reactivity of an activated thiolester within these proteins. Autolytic cleavage occurs by internal nucleophilic attack on one face of the planar thiolester, while the covalent binding reaction of the activated proteins follows exposure of the opposite face of the thiolester to attack by external nucleophiles. Although the autolytic cleavage reaction does not occur under physiological conditions, the study of this phenomenon has provided valuable evidence in support of the mechanisms postulated for the physiological covalent binding reactions. The ease with which autolysis can be induced and observed in C3, C4, and alpha 2 M has provided a valuable method for detecting the active forms of these proteins in circumstances where other assays are impracticable, as, for example, in the examination of the uptake of active C3 by lymphocytes. Autolytic cleavage has also been used by Karp and colleagues to produce fragments used in characterizing genetic and biosynthetic variants of mouse C4 and the mouse protein Slp, which is structurally similar to C4. Gross structural comparisons made among C3, C4, and alpha 2 M on the basis of alignment of the autolytic cleavage sites and the protease-activation sites in these proteins were useful in predicting how the alpha-, beta-, and gamma-chains of C4, or the alpha- and beta-chains of C3, were aligned in the single polypeptide chain pro-forms of these proteins. The beta-alpha-gamma alignment deduced for C4 was also found by Goldberger and Colten. Similar alignments of cleavage sites have been used as a basis for evolutionary comparisons of complement proteins and alpha 2 M from species other than man. Although autolytic cleavage has been described only for C3, C4, alpha 2 M, and Slp, it is likely that other proteins will be found that exhibit this phenomenon. A possible candidate is pregnancy-associated plasma protein A (PAPP-A) which resembles alpha 2 M in many respects. The autolytic cleavage reaction will serve as a useful indicator in the detection of other proteins that undergo covalent binding by the mechanism discussed above.

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Human α2-macroglobulin : time dependent degradation under denaturing conditions

Cited by 3 publications

References 29 publications

Mouse α-macroglobulin. Structure, function and a molecular model

Mouse α-macroglobulin. Structure, function and a molecular model

Isolation and characterization of horse α2-macroglobulin protease inhibitor

Autolytic Fragmentation of Complement Components C3 and C4 and Its Relationship to Covalent Binding Activity

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