Welcome to the home page of the Horwich lab at Yale School of Medicine, Dept. of Genetics, and Howard Hughes Medical Institute. We're interested in a family of molecular machines called chaperonins that mediate ATP-dependent protein folding in the cell.
Address: Art Horwich
Yale School of Medicine
145 Boyer Center for Molecular Medicine
295 Congress Ave.
New Haven CT, 06510
Phone: (203) 737-4431
FAX: (203)
737-1761
e-mail: horwich@csb.yale.edu
In 1987, during a genetic screen in yeast, we stumbled across a protein folding function inside mitochondria. In the mutant strain, proteins entered mitochondria from the cytosol normally but then misfolded and aggregated. The gene affected encoded a 60 kDa protein that we named Hsp60 because it was mildly heat inducible. Hsp60 is found in an 850 kDa double ring assembly, each ring containing 7 copies of Hsp60.
Such assemblies, called chaperonins, also exist in other cellular compartments and are essential components, mediating protein folding under both heat shock and normal conditions. Ever since 1987, we've been studying these fascinating molecules both in vivo and in vitro, with particular emphasis on the Hsp60 homologue in E. coli known as GroEL. We and others found early on that a chaperonin-mediated folding reaction can be reconstituted in a test tube, and that has enabled structural and functional studies that have begun to explain how chaperonins work. In particular, a combination of crystallographic studies, with the late Paul Sigler's group here at Yale, and functional studies, using dynamic studies of a variety of mutant chaperonins, have begun to reveal how these chaperonins work. The schematic diagram below summarizes our current view of the chaperonin-mediated protein folding pathway.
Publications
Other Web Resources:
Boyer Center for Molecular Medicine
Center for Structural Biology
Howard Hughes Medical Institute
The Scripps Research Institute
X-ray Facility
Yale School of Medicine
Yale University
Lab People:
Fernando Agarraberes, Postdoc, BCMM 143 ------------------------737-4428
Eli Chapman, Postdoc, Scripps --------------------------------------858-784-7387
George Farr, Staff Scientist, BCMM 143 -----------------------------737-4428
Wayne Fenton, Res. Scientist, BCMM 143 ---------------------------737-4428
Scripps
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Krystyna Furtak, Res. Tech., BCMM 145 ----------------------------737-4431
Jörg Hinnerwisch, Postdoc, Scripps --------------------------------858-784-7387
Art Horwich, Prof., BCMM 145
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Scripps
------------------------------858-784-7386
Eda Koculi, Postdoc, Scripps ----------------------------------------858-784-7387
Eunice (Eun Sun) Park, Postdoc, BCMM 143 ------------------------737-4428
Jiou Wang, Postdoc, BCMM 145 ----------------------------------------737-4431
Note that some of us are located at The Scripps Research Institute in La
Jolla, CA.
If you have comments or suggestions, email me at wayne.fenton@yale.edu
phone: 203-737-4431
fax: 203-737-1761