tailieunhanh - Báo cáo khoa học: R120G aB-crystallin promotes the unfolding of reduced a-lactalbumin and is inherently unstable

a-Crystallin is the principal lens protein which, in addition to its structural role, also acts as a molecular chaperone, to prevent aggregation and preci-pitation of other lens proteins. One of its two subunits,aB-crystallin, is also expressed in many nonlenticular tissues, and a natural missense muta-tion, R120G, has been associated with cataract and desmin-related myopa- | ềFEBS Journal R120G aB-crystallin promotes the unfolding of reduced a-lactalbumin and is inherently unstable Teresa M. Treweek1 2 Agata Rekas1 Robyn A. Lindner1 z Mark J. Walker2 J. Andrew Aquilina1 3 Carol V. Robinson3 Joseph Horwitz4 Ming Der Perng5 Roy A. Quinlan5 and John A. Carver1 1 Department of Chemistry University of Wollongong NSW Australia 2 Department of BiologicalSciences University of Wollongong NSW Australia 3 Department of Chemistry University of Cambridge UK 4 Jules Stein Eye Institute University of California Los Angeles Schoolof Medicine Los Angeles CA USA 5 Schoolof Biologicaland BiomedicalSciences University of Durham UK Keywords cataract lens proteins molecular chaparone protein aggregation protein unfolding Correspondence J. A. Carver Schoolof Chemistry and Physics University of Adelaide South Australia 5005 Australia Fax 61 8 8303 4380 Tel 61 8 8303 3110 E-mail Present address Proteome Systems Ltd Unit 1 35-41 Waterloo Road North Ryde NSW 2113 Australia Received 8 September 2004 revised 21 November 2004 accepted 29 November 2004 doi a-Crystallin is the principal lens protein which in addition to its structural role also acts as a molecular chaperone to prevent aggregation and precipitation of other lens proteins. One of its two subunits aB-crystallin is also expressed in many nonlenticular tissues and a natural missense mutation R120G has been associated with cataract and desmin-related myopathy a disorder of skeletal muscles Vicart P Caron A Guicheney P Li Z Prevost MC Faure A Chateau D Chapon F Tome F Dupret JM Paulin D Fardeau M 1998 Nat Genet 20 92-95 . In the present study realtime 1H-NMR spectroscopy showed that the ability of R120G aB-crystallin to stabilize the partially folded molten globule state of a-lactalbumin was significantly reduced in comparison with wild-type aB-crystallin. The mutant showed enhanced interaction with and promoted unfolding of reduced a-lactalbumin