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Dissociation of m-calpain subunits occurs after autolysis of the N-terminus of the catalytic subunit, and is not required for activation.

Dissociation of m-calpain subunits occurs after autolysis of the N-terminus of the catalytic subunit, and is not required for activation. Research Abstract Details 

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  • Dissociation of m-calpain subunits occurs after autolysis of the N-terminus of the catalytic subunit, and is not required for activation. Abstract Text:

    k nakagawaK Nakagawa,h masumotoH Masumoto,h sorimachiH Sorimachi,k suzukiK Suzuki,

    Calpain is a heterodimeric, intracellular Ca(2+)-dependent, "bio-modulator" that alters the properties of substrates through site-specific proteolysis. It has been proposed that calpains are activated by autolysis of the N-terminus of the large subunit and/or its dissociation into the subunits. It is, however, unclear whether the dissociation into subunits is required for the expression of protease activity and/or for in vivo function. Recently, the crystal structure of m-calpain in the absence of Ca(2+) has been resolved. The 3D structure clearly shows that the N-terminus of the m-calpain large subunit (mCL) makes contact with the 30K subunit, suggesting that autolysis of the N-terminus of mCL changes the interaction of both subunits. To examine the relationship between autolysis, dissociation, and activation, we made and analysed a series of N-terminal mutants of mCL that mimic the autolysed forms or have substituted amino acid residue(s) interacting with 30K. As a result, the mutant m-calpains, which are incapable of autolysis, did not dissociate into subunits, whereas those lacking the N-terminal 19 residues (Delta 19), but not those lacking only nine residues (Delta 9), dissociated into subunits even in the absence of Ca(2+). Moreover, both Delta 9 and Delta 19 mutants showed an equivalent reduced Ca(2+) requirement for protease activity. These results indicate that autolysis is necessary for the dissociation of the m-calpain subunits, and that the dissociation occurs after, but is not necessary for, activation.

    Dissociation of m-calpain subunits occurs after autolysis of the N-terminus of the catalytic subunit, and is not required for activation. Publishing Authors By Initials

    k nakagawaK Nakagawa,h masumotoH Masumoto,h sorimachiH Sorimachi,k suzukiK Suzuki,

    For similar proteins: protein subunits research abstracts see: proteins: protein subunits research

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    Dissociation of m-calpain subunits occurs after autolysis of the N-terminus of the catalytic subunit, and is not required for activation. Journal Published:

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: Journal of biochemistry

    VOLUME: 130

    Page Numbers: 605-11

    Journal Abbreviation: J. Biochem.

    ISSN: 0021-924X

    DAY: 19

    MONTH: Nov

    YEAR: 2001

    Dissociation of m-calpain subunits occurs after autolysis of the N-terminus of the catalytic subunit, and is not required for activation. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 376600

    Dissociation of m-calpain subunits occurs after autolysis of the N-terminus of the catalytic subunit, and is not required for activation. Keywords Mesh Terms:

    KEYWORDS: Protein Subunits

    MESH TERMS: cytology

    Chemical & Substance for Abstract: Dissociation of m-calpain subunits occurs after autolysis of the N-terminus of the catalytic subunit, and is not required for activation. Information

    Substance Name: Calpain

    Registry Number: EC 3.4.22.-

    Grant and Affiliation Information for Dissociation of m-calpain subunits occurs after autolysis of the N-terminus of the catalytic subunit, and is not required for activation.

    AFFILIATION: Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.

    Country: Japan

    Japan Research PublicationJapan Research Publication

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    MEDLINETA: J Biochem

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