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Members of my group |
Much of our work has centered on analysis of cooperativity in the GroE chaperonin system (for reviews see Horovitz et al., 2001; Horovitz and Willison, 2005). Steady-state and presteady-state kinetic data led us to propose several years ago a nested allosteric model for the GroEL double-ring (Yifrach and Horovitz, 1995). According to this model, each ring of GroEL is in equilibrium between a T state (with low affinity for ATP and high affinity for protein substrates) and an R state (with high affinity for ATP and low affinity for protein substrates), in accordance with the concerted Monod-Wyman-Changeux model. A second level of allostery is reflected in inter-ring negative cooperativity which is described by the sequential Koshland-Nemethy-Filmer model. The three allosteric states of GroEL in the presence of ATP, TT, TR and RR, have been visualized  using cryo-EM (White et al., 1997). We are currently analysing the allosteric mechanism of CCT, the eukaryotic homologue of GroEL. Each ring of CCT is composed of 8 different subunits in contrast to the 7 identical subunits of GroEL rings. Steady-state kinetic data for CCT shows that it also undergoes two ATP-induced allosteric transitions which, in contrast to GroEL, are not concerted (Kafri et al., 2001; Rivenzon-Segal et al., 2005). Specific research questions we are addressing at the present time are:
1. What is the relationship between allostery in the GroE chaperonin system and its folding function? 2. What is the pathway(s) of the ATP-induced allosteric transitions of GroEL? |
 Cryo-EM images of the TT (left) and RR (right) allosteric states of GroEL at
30 Ċ resolution (Prof. H. Saibil, Birkbeck College).
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| Selected Publications |
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Aharoni, A. and Horovitz, A. (1996) J. Mol. Biol. 258, 732-735. |  |
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Aharoni, A. and Horovitz, A. (1997) Proc. Natl. Acad. Sci. U. S. A. 94, 1698-1702. | |
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Amir, A. and Horovitz, A. (2004) J Mol. Biol. 338, 979-988. | |
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Danziger, O., Rivenzon-Segal, D., Wolf, SG. and Horovitz A. (2003) Proc. Natl. Acad. Sci. U. S. A. 100, 13797-13802. | |
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Danziger, O., Shimon L. and Horovitz, A. (2006) Protein Sci. 15, 1270-1276. | |
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Fridmann, Y., Kafri, G., Danziger, O. and Horovitz, A. (2002) Biochemistry 41, 5938-5944 |
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Fridmann, Y., Ulitzur, S. and Horovitz, A. (2000) J. Biol. Chem. 275, 37951-37956. | |
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Horovitz, A. (1996) Folding & Design 1, R121-R126. | |
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Horovitz, A. and Yifrach, O. (2000) Bull. Math. Biol. 62, 241-246. | |
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Horovitz, A., Fridmann, Y., Kafri, G. and Yifrach, O. (2001) J. Struct. Biol. 135, 104-114. | |
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Horovitz, A., Amir, A., Danziger, O. and Kafri, G. (2002) Proc. Natl. Acad. Sci. U.S.A. 99, 14095-14097. | |
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Horovitz, A. and Willison, KR. (2005) Curr. Opin. Struct. Biol. 15, 646-651. | |
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Inbar, E. and Horovitz, A. (1997) Biochemistry 36, 12276-12281. | |
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Jacob E., Horovitz A. and Unger R. (2007) Bioinformatics 23, i240-i248. | |
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Kafri, G., Willison, K. R. and Horovitz, A. (2001) Protein Sci. 10, 445-449. | |
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Kafri, G. and Horovitz, A. (2003) J. Mol. Biol. 326, 981-987. | |
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Kass, I. and Horovitz, A. (2002) Proteins: Struct., Funct. & Genet. 48, 611-617. | |
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Kipnis Y., Papo N., Haran G. and Horovitz A. (2007) Proc. Natl. Acad. Sci. U. S. A. 104, 3119-3124. | |
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Noivirt, O., Eisenstein, M. and Horovitz, A. (2005) Protein Eng. Des. Sel. 18, 247-253. | |
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Papo N., Kipnis Y., Haran G. and Horovitz A. (2008) J. Mol. Biol. 380, 717-725. | |
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Rivenzon-Segal, D., Wolf, SG, Shimon, L., Willison, KR. and Horovitz, A. (2005) Nat. Struct. Mol. Biol. 12, 233-237. | |
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Shimon L., Hynes G. M., McCormack E. A., Willison K. R. and Horovitz A. (2008) J. Mol. Biol. 377, 469-477. | |
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White, Chen, S., Roseman, A. M., Yifrach, O., Horovitz, A. and Saibil, H. R. (1997) Nat. Struct. Biol. 4, 690-694. | |
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Yifrach, O. and Horovitz, A. (1995) Biochemistry 34, 5303-5308. | < |
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Yifrach, O. and Horovitz, A. (1998) J. Amer. Chem. Soc. 120, 13262-13263. | |
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Yifrach, O. and Horovitz, A. (2000) Proc. Natl. Acad. Sci. U. S. A. 97, 1521-1524. | |