This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The two Ca2+-dependent cysteine proteases, ?- and ?-calpain, are involved in various Ca2+-linked signal pathways, but differ markedly in their Ca2+ requirements for activation. Using diffraction data collected at CHESS, we have determined the structure of a ?-like calpain, which has 85% ?-calpain sequence (the first 48 and the last 62 residues of the large subunit are those from m-calpain) and a low Ca2+ requirement. This construct was used because ?-calpain itself is too poorly expressed. The structure of ?-like calpain is very similar in overall fold to that of m-calpain as expected, but differs significantly in two aspects. In comparison with m-calpain, the catalytic triad residues in ?-like calpain, His and Cys, are much closer together in the absence of Ca2+;and significant portions of the Ca2+-binding EF-hand motifs are disordered and more flexible. These structural differences imply that Ca2+-free ?-calpain may represent a partially activated structure, requiring lower Ca2+ concentration to trigger its activation

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001646-29
Application #
8363515
Study Section
Special Emphasis Panel (ZRG1-BCMB-E (40))
Project Start
2011-07-01
Project End
2012-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
29
Fiscal Year
2011
Total Cost
$17,577
Indirect Cost
Name
Cornell University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
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