Pascal F Egea, Ph.D.

Mailing Address:
Box 951737
BSRB 330
615 Charles E. Young Drive South
Los Angeles, CA 90095

Office Address:
Boyer Hall room 356 611 Charles E Young Drive East
Los Angeles, CA 90095

Affiliations
Affiliations
Assistant Professor, Biological Chemistry
Member, Biochemistry, Biophysics & Structural Biology GPB Home Area
Research Interests

Membrane proteins constitute about 30% of all genome-encoded proteins and are targets for over 40% of all drugs in use today. While the number of membrane protein structure increases, providing valuable insights into their architecture and function, the molecular mechanisms governing their proper localization, assembly and insertion into biological membranes still remain elusive. Protein export and secretion is essential to life and all living cells have developed sophisticated machineries and subtle regulation mechanisms, and spend considerable energy to ensure proper targeting, folding and assembly of this particular class of proteins.

We are interested in the study of different membrane protein targeting and translocation systems in all three kingdoms of life (Bacteria, Archea and, Eukarya) and we primarily use X-ray crystallography in combination with other biophysical techniques to unravel the general molecular mechanisms that govern the proper targeting, folding and insertion of membrane proteins. On the long-term, we also seek to develop inhibitors of these systems that could be used as anti-bacterial, anti-fungal, anti-parasitic and anti-cancer drugs.

Biography

Pascal Egea received is B.S. in Molecular and Cellular Biology from the Ecole Normale Supérieure de Lyon (Lyon, France) in 1991. He then went to graduate school at the Université Louis Pasteur (Strasbourg, France) where he studied the structure and function of the retinoic acid receptors in the laboratory of Dr Dino Moras. After completing is Ph.D. in 1999, Pascal went to the University of California in San Francisco for post-doctoral training under the co-mentorship of Professors Robert Stroud and Peter Walter; during this period he studied the signal recognition particle and protein translocation pathways. Pascal joined the Department of Biological Chemistry as an assistant professor in the fall of 2009.

Publications
AhYoung Andrew P, Jiang Jiansen, Zhang Jiang, Khoi Dang Xuan, Loo Joseph A, Zhou Z Hong, Egea Pascal F Conserved SMP domains of the ERMES complex bind phospholipids and mediate tether assembly. Proceedings of the National Academy of Sciences of the United States of America. 2015; .
Gold Daniel A, Kaplan Aaron D, Lis Agnieszka, Bett Glenna C L, Rosowski Emily E, Cirelli Kimberly M, Bougdour Alexandre, Sidik Saima M, Beck Josh R, Lourido Sebastian, Egea Pascal F, Bradley Peter J, Hakimi Mohamed-Ali, Rasmusson Randall L, Saeij Jeroen P J The Toxoplasma Dense Granule Proteins GRA17 and GRA23 Mediate the Movement of Small Molecules between the Host and the Parasitophorous Vacuole. Cell host & microbe. 2015; 17(5): 642-52.
Peng Mindy, Cascio Duilio, Egea Pascal F Crystal structure and solution characterization of the thioredoxin-2 from Plasmodium falciparum, a constituent of an essential parasitic protein export complex. Biochemical and biophysical research communications. 2015; 456(1): 403-9.
Egea Pascal F, Muller-Steffner Hélène, Kuhn Isabelle, Cakir-Kiefer Céline, Oppenheimer Norman J, Stroud Robert M, Kellenberger Esther, Schuber Francis Insights into the mechanism of bovine CD38/NAD+glycohydrolase from the X-ray structures of its michaelis complex and covalently-trapped intermediates. PloS one. 2012; 7(4): e34918.
Korennykh Alexei V, Egea Pascal F, Korostelev Andrei A, Finer-Moore Janet, Stroud Robert M, Zhang Chao, Shokat Kevan M, Walter Peter Cofactor-mediated conformational control in the bifunctional kinase/RNase Ire1. BMC biology. 2011; 9: 48.
Korennykh Alexei V, Korostelev Andrei A, Egea Pascal F, Finer-Moore Janet, Stroud Robert M, Zhang Chao, Shokat Kevan M, Walter Peter Structural and functional basis for RNA cleavage by Ire1. BMC biology. 2011; 9: 47.
Brown Christopher M, Ray Manisha, Eroy-Reveles Aura A, Egea Pascal, Tajon Cheryl, Craik Charles S Peptide length and leaving-group sterics influence potency of peptide phosphonate protease inhibitors. Chemistry & biology. 2011; 18(1): 48-57.
Egea Pascal F, Stroud Robert M Lateral opening of a translocon upon entry of protein suggests the mechanism of insertion into membranes. Proceedings of the National Academy of Sciences of the United States of America. 2010; .
Korennykh, A. V. Egea, P. F. Korostelev, A. A. Finer-Moore, J. Zhang, C. Shokat, K. M. Stroud, R. M. Walter, P. The unfolded protein response signals through high-order assembly of Ire1. Nature. 2009; 457(7230): 687-93.
Farady, C. J. Egea, P. F. Schneider, E. L. Darragh, M. R. Craik, C. S. Structure of an Fab-protease complex reveals a highly specific non-canonical mechanism of inhibition. J Mol Biol. 2008; 380(2): 351-60.
Egea, P. F. Napetschnig, J. Walter, P. Stroud, R. M. Structures of SRP54 and SRP19, the two proteins that organize the ribonucleic core of the signal recognition particle from Pyrococcus furiosus. PLoS One. 2008; 3(10): e3528.
Egea, P. F. Tsuruta, H. de Leon, G. P. Napetschnig, J. Walter, P. Stroud, R. M. Structures of the signal recognition particle receptor from the archaeon Pyrococcus furiosus: implications for the targeting step at the membrane. PLoS One. 2008; 3(11): e3619.
Egea, P. F. Stroud, R. M. Walter, P. Targeting proteins to membranes: structure of the signal recognition particle. Curr Opin Struct Biol. 2005; 15(2): 213-20.
Chu, F. Shan, S. O. Moustakas, D. T. Alber, F. Egea, P. F. Stroud, R. M. Walter, P. Burlingame, A. L. Unraveling the interface of signal recognition particle and its receptor by using chemical cross-linking and tandem mass spectrometry. Proc Natl Acad Sci U S A. 2004; 101(47): 16454-9.
Egea, P. F. Shan, S. O. Napetschnig, J. Savage, D. F. Walter, P. Stroud, R. M. Substrate twinning activates the signal recognition particle and its receptor. Nature. 2004; 427(6971): 215-21.
Savage, D. F. Egea, P. F. Robles-Colmenares, Y. O'Connell, J. D., 3rd Stroud, R. M. Architecture and selectivity in aquaporins: 2.5 a X-ray structure of aquaporin Z. PLoS Biol. 2003; 1(3): E72.
Egea, P. F. Mitschler, A. Moras, D. Molecular recognition of agonist ligands by RXRs. Mol Endocrinol. 2002; 16(5): 987-97.
Rochel, N. Tocchini-Valentini, G. Egea, P. F. Juntunen, K. Garnier, J. M. Vihko, P. Moras, D. Functional and structural characterization of the insertion region in the ligand binding domain of the vitamin D nuclear receptor. Eur J Biochem. 2001; 268(4): 971-9.
Egea, P. F. Moras, D. Purification and crystallization of the human RXRalpha ligand-binding domain-9-cisRA complex. Acta Crystallogr D Biol Crystallogr. 2001; 57(Pt 3): 434-7.
Egea, P. F. Rochel, N. Birck, C. Vachette, P. Timmins, P. A. Moras, D. Effects of ligand binding on the association properties and conformation in solution of retinoic acid receptors RXR and RAR. J Mol Biol. 2001; 307(2): 557-76.
Egea, P. F. Klaholz, B. P. Moras, D. Ligand-protein interactions in nuclear receptors of hormones. FEBS Lett. 2000; 476(1-2): 62-7.
Egea, P. F. Mitschler, A. Rochel, N. Ruff, M. Chambon, P. Moras, D. Crystal structure of the human RXRalpha ligand-binding domain bound to its natural ligand: 9-cis retinoic acid. Embo J. 2000; 19(11): 2592-601.