RGD Reference Report - Activation of calpain by Ca2+: roles of the large subunit N-terminal and domain III-IV linker peptides. - Rat Genome Database

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Activation of calpain by Ca2+: roles of the large subunit N-terminal and domain III-IV linker peptides.

Authors: Hosfield, CM  Elce, JS  Jia, Z 
Citation: Hosfield CM, etal., J Mol Biol. 2004 Oct 29;343(4):1049-53.
RGD ID: 11041056
Pubmed: PMID:15476820   (View Abstract at PubMed)
DOI: DOI:10.1016/j.jmb.2004.08.073   (Journal Full-text)

The calpains are a family of cysteine proteases with closely related amino acid sequences, but a wide range of Ca(2+) requirements (K(d)). For m-calpain, K(d) is approximately 325microM, for mu-calpain it is approximately 50microM, and for calpain 3 it is not strictly known but may be approximately 0.1microM. On the basis of previous structure determination of m-calpain we postulated that two regions of the calpain large subunits, the N-terminal peptide (residues 1-20) and a domain III-IV linker peptide (residues 514-530 in m-calpain) were important in defining K(d). The mutations Lys10Thr in the N-terminal peptide, and Glu517Pro in the domain linker peptide, reduced K(d) of m-calpain by 30% and 42%, respectively, revealing that these two regions are functionally important. The increased Ca(2+)-sensitivity of these mutants demonstrate that the Lys10-Asp148 salt link and the short beta-sheet interaction involving Glu517 are factors contributing to the high K(d) of m-calpain. Though these two regions are physically remote from the active site and Ca(2+)-binding site, they play significant roles in regulating the response of calpain to Ca(2+). Differences in these interactions in mu-calpain and in calpain 3 are also consistent with their progressively lower K(d) values.



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Capn2Ratprotein binding enablesIPIUniProtKB:Q64537PMID:15476820IntAct 
Capns1Ratprotein binding enablesIPIUniProtKB:Q07009PMID:15476820IntAct 

Objects Annotated

Genes (Rattus norvegicus)
Capn2  (calpain 2)
Capns1  (calpain, small subunit 1)


Additional Information