Cellular and Structural Biochemistry - Michel VERON
Activities of the Unit
We address 2 projects both with extensive R&D attached programs aimed at designing new anti-cancer and analgesic drugs.
(i) The "NEMO group" of Fabrice AGOU, studies a crucial regulatory protein of the NF-kB pathway involved in cancer progression. Mutations in NEMO are also associated with rare human diseases. We study NEMO structure and analyze how pathologic mutations alter ubiquitin mediated transduction events by combining structural, biochemical and cell biology techniques.
(i) The "NEMO group" of Fabrice AGOU, studies a crucial regulatory protein of the NF-kB pathway involved in cancer progression. Mutations in NEMO are also associated with rare human diseases. We study NEMO structure and analyze how pathologic mutations alter ubiquitin mediated transduction events by combining structural, biochemical and cell biology techniques.
| CC2-LZ domain of NEMO |
Ubiquitine bound to the ZF domain of NEMO |
(ii) The "Opiorphin group" of Catherine ROUGEOT characterizes Opiorphin, a human physiological dual inhibitor of both enkephalin-inactivating Zn-ectopeptidases, NEP and AP-N. Opiorphin, a powerful pentapeptide inhibitor of pain with a analgesic potency similar to morphine, is also a modulator of well-being behavior in rat models.
| in silico representative image of the QRFSR-peptide Opiorphin 2D structure, in blue: Glutamine, Q; red: Arginine, R; green: Phenylalanine, F; yellow: Serine, S |
The three most significant publications
1. Grubisha, O., Kaminska, M., Duquerroy, S., Fontan, E., Cordier, F., Haouz, A., Raynal, B., Chiravalli, J., Delepierre, M., Israël, A., Véron, M. and Agou, F. (2010) DARPin-assisted crystallography of the CC2-LZ domain of NEMO reveals a coupling between dimerization and ubiquitin-binding. J. Mol. Biol.: 395. 89-104.
2. Laplantine, E., Fontan, E., Chiaravalli, J., Lopez, T., Lakisic, G., Véron, M., Agou, F. and Israël, A. (2009) NEMO specifically recognizes K63-linked poly-ubiquitin chains through a new bipartite ubiquitin-binding domain. EMBO J., 28, 2885-2895.
3. Wisner, A., Dufour, E., Messaoudi, M., Nejdi, A., Marcel, A., Ungeheuer, M. N. and Rougeot, C. (2006). Human Opiorphin, a natural antinociceptive modulator of opioid-dependent pathways. Proc. Natl. Acad. Sci. U S A 103, 17979-17984.