PRINCIPAL SCIENTIST
 Nogales, E

 POSTDOCTORAL FELLOWS
 Galburt, E
Leschziner, A
Meurer-Grob, P
Wang, H

 STUDENTS
 Kang, M
Kostek, S
Niederstrasser, H
Shreter, R
Siridechadilok, B

 STAFF
 Avila-Sakar, A
Cruse, M
Fang, J
Lipscomb, S
Peris, M
Tucker, T

 


The overall research theme in my lab is the structural characterization of complex biological assemblies, their architecture, interactions with different ligands, and the regulation of their assembly and function. Our work centers around two main projects: the structural basis of microtubule dynamics and the structural organization of the human transcriptional initiation machinery. We are using electron microscopy, image analysis, homology modeling, and functional biochemical assays to gain new information on these systems and to progress towards models of how they are regulated in the cell.

We are applying cryo-electron microscopy (cryo-EM) and image analysis to characterize the structure and assembly of microtubules and their interaction with cellular factors and antimitotic ligands. The atomic model of tubulin that we obtained by electron crystallography has allowed us to establish the structural basis of nucleotide exchange and polymerization-coupled hydrolysis. The high-resolution model of the microtubule, on the other hand, has allowed us to propose a mechanism for the hydrolysis-induced depolymerization of microtubules. We are now characterizing the conformational change in tubulin that triggers microtubule disassembly following GTP hydrolysis, as well as the interaction of tubulin with the cellular microtubule depolymerizer XKCM1.

We are also pursuing the structures of the eukaryotic, general transcriptional machinery TFIID and its interaction with activators and cofactor complexes. We obtained a 3-D model of TFIID and its complex with TFIIA and TFIIB, and used antibody labeling to locate the position of TBP within the complex. More recently we have obtained 3D reconstructions of the large human cofactor complexes ARC and CRSP. Our EM analysis of independently derived CRSP complexes has revealed multiple distinct conformations induced by different activators. We are now extending these studies to the structural characterization of the whole transcription preinitiation complexes, of chromatin remodeling factors, and of molecular machineries involved in transcription-coupled DNA repair.

Eva Nogales de la Morena
Faculty Scientist/
Life Sciences Division

UC Berkeley
355 LSA
Berkeley, CA 94720-3200
office tel: (510)642-0557
lab tel: (510)642-2222
assistant tel: (510)643-6411
fax: (510)642-8806
email: ENogales@lbl.gov
 

 

Nogales Laboratory Information

Recent Publications

Li, H., DeRosier, D., Nogales, E. and Downing, K.H. (2002). “Structure
of the microtubule at 8 Å resolution”, Structure, in press.

Näär, A. M., Taatjes, D. J., Zhai, W., Nogales E. and Tjian, R. (2002)
Human CRSP interacts with RNA Polymerase II CTD and adopts a Specific
CTD-bound Conformation. Genes Dev 16, 1339-1344.

Niederstrasser, H., Salehi-Had, H., Walczak, C. and Nogales, E. (2002)
“Effects of XKCM1 on different tubulin polymers”, J. Mol. Biol. 316, 815-826.

Taatjes, D., Näär, A.R., Andel, F., Nogales, E. and Tjian, R. (2002)
“Structural and Functional studies of transcriptional cofactors”,
Science 295, 1058-1062.

Löwe, J., Li, H., Downing, K.H., and Nogales, E. (2001) “Refined
structure of ab tubulin at 3.5 Å”, J. Mol. Biol. 313, 1083-1095.

Avila-Sakar, A., Misaghi, S., Wilson-Kubalek, E., Zgurskaya, H.,
Nikaido, H., Downing, K.H. and Nogales, E. (2001) “Structure of AcrA,
the periplasmic component of a bacterial multidrug efflux pump,
crystallized on lipid layers”, J. Struct. Biol. 136, 81-84.

Snyder, J. P., Nettles, J. H., Cornett, B., Downing, K. H. and Nogales,
E. (2001) “The binding conformation of taxol in beta tubulin and a
proposal for its effect on lateral polymerization”, PNAS 98, 5312-5316.

Inclán, Y. and Nogales, E. (2001) “Potential for self-assembly and
microtubule interaction of g-, d- and e-tubulin”, J. Cell Sci. 114,
413-422.

Paluh, J. L., Nogales, E., Oakley, B. R., McDonald, K., Pidoux, A. L.
and Cande, W. Z. (2000), “A mutation in g-tubulin alters microtubule
dynamics and organization and is synthetically lethal with the
kinesin-like protein Pkl1p”, Mol. Cell Biol. 11, 1225-1239.

Giannakakou, P., Gussio, R., Nogales, E., Downing, K. H., Zaharevitz,
D., Poy, G., Nicolau, K. C. and Fojo, T. (2000), “A common pharmacophore
for epothilone and taxol: molecular basis for drug resistance-conferred
by tubulin mutations in human cancer cells”,PNAS 97, 2904-2909.

Andel, F., Ladurner, A. G., Inouye, C., Tjian, R. and Nogales, E (1999)
“Three-dimensional structure of the human TFIID-TFIIA-TFIIB complex”,
Science 286, 2153-2156.

Nogales, E., Whittaker, M., Milligan R. A., & Downing, K. H. (1999),
“High resolution model of the microtubule”, Cell 96, 79-88.

Nogales, E., Downing, K. H., Amos, L. A., & Lowe, J. Y. (1998), “Tubulin
and FtsZ form a distinct family of GTPases”, Nature Struct. Biol. 5, 451-458.

Nogales, E., Wolf, S. G., & Downing, K. H. (1998), “Structure of the ab
tubulin dimer by electron crystallography”, Nature, 391, 199-203.