TAILIEUCHUNG - Báo cáo khoa học: Distinguishing between calpain heterodimerization and homodimerization

Human P-glycoprotein is an ATP-binding cassette transporter that plays an important role in the defence against potentially harmful molecules from the environment. It is involved in conferring resistance against cancer therapeutics and plays an important role for the pharmacokinetics of drugs. | ỊFEBS Journal Distinguishing between calpain heterodimerization and homodimerization Ravikiran Ravulapalli1 Robert L. Campbell1 Sherry Y. Gauthier1 Sirano Dhe-Paganon2 and Peter L. Davies1 1 Department of Biochemistry Queen s University Kingston Canada 2 StructuralGenomics Consortium and the Department of Physiology University of Toronto Canada Keywords calcium calpain dimerization EF-hand protease Correspondence P. L. Davies Department of Biochemistry Queen s University Kingston ON K7L 3N6 Canada Fax 1 613 533 2497 Tel 1 613 533 2983 E-mail daviesp@ Received 28 August 2008 revised 13 November 2008 accepted 4 December 2008 doi The two main mammalian calpains 1 and 2 are heterodimers of a large 80 kDa and a small 28 kDa subunit that together bind multiple calcium ions during enzyme activation. The main contact between the two subunits of these intracellular cysteine proteases is through a pairing of the fifth EF-hand of their C-terminal penta-EF-hand PEF domains. From modeling studies and observation of crystal structures it is not obvious why these calpains form heterodimers with the small subunit rather than homodimers of the large subunit as suggested for calpain 3 p94 . Therefore we have used a differential tagging system to determine which of the other PEF domain-containing calpains form heterodimers and which form homodimers. His6-tagged PEF domains of calpains 1 3 9 and 13 were coexpressed with the PEF domain of the small subunit that had been tagged with an antifreeze protein. As predicted the PEF domain of cal-pain 1 heterodimerized and that of calpain 3 formed a homodimer. The PEF domain of digestive tract-specific calpain 9 heterodimerized with the small subunit and that of calpain 13 prevalent in lung and testis was mainly found as a homodimer with a small amount of heterodimer. These results indicate whether recombinant production of a particular calpain requires coexpression of the small subunit and whether .

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