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Arthur Horwich

 

Molecular Cell Biology, Genetics & Development; Molecular Biophysics & Biochemistry

Professor of Genetics and Pediatrics

Education

A.B. Brown University 1972
M.D. Brown University 1975

Research Interests

We are studying protein folding and misfolding in the cell, along three lines: 1) Examining how “chaperonin” ring structures mediate ATP-dependent folding of a large number of newly-translated proteins. Chaperonins bind polypeptides through exposed hydrophobic surfaces, then carry out productive folding in an encapsulated hydrophilic chamber. We are studying what happens to “substrate” proteins during this process. 2) Studying the mechanism of action of an “opposite number,” an ATP-dependent chaperone unfoldase called ClpA, which binds native proteins in a central channel and then pulls them apart during ATP-dependent translocation through the channel. We are studying how much force is involved in mediating such unfolding and are seeking to observe at the single molecule level whether protein unraveling occurs progressively or concertedly. 3) Studying a misfolding disease, SOD-linked ALS (Lou Gehrig’s Disease), using mouse and worm models, employing both genetics and biochemistry to understand why SOD misfolding causes motor neuron damage.

Links

• Horwich Homepage

Recent Publications

• Elad, N., Farr, G.W., Clare, D.K., Orolova, E.V., Horwich, A.L., and Saibil, H.R. (2007). Topologies of a substrate protein bound to the chaperonin GroEL. Mol. Cell (In press).
• Park, E.S., Fenton, W.A., and Horwich, A.L. (2007). Disulfide bond formation as probe of topology during folding in the GroEL-GroES chamber: Correct formation of long-range bonds and editing of incorrect short-range ones. Proc. Natl. Acad. Sci. (USA) 104:2145-2150.

Contact

E-mail
arthur.horwich@yale.edu