|
|
 |
|
| David Eisenberg - | |
|
|
David Eisenberg, Michael Strong, Markus Kauffman, Debnath Pal,
Sulmin Kim, Celia Goulding, Peter Bowers, Matteo Pellegrini.
Howard Hughes Medical Institute, Box 951570, UCLA, Los Angeles
CA 90095-1570.
Structural genomics has been defined as structural biology on
a genome-wide scale. Because many, if not most, cellular
proteins act as members of complexes, structural genomics
should include the study of protein complexes, but to date
most of the emphasis of this new science has been on the
structures of individual proteins. Even if structural
scientists are interested principally in the structures
of individual proteins, undertaking studies of complexes
may be helpful, because some proteins express, purify,
and crystallize well only in the company of their natural
partners.
By analysis of genome sequences (1,2), we have inferred pairs
and larger clusters of proteins that are functionally linked.
By comparing to these inferred functional linkages to
databases of complexes and pathways, we find that many of the
proteins inferred to be linked to others are in fact binding
partners (2.3). Methods of inference used include Rosetta
Stone (4), Phylogenetic Profiles (5), Gene Neighbor and
Operon (6), and DNA microarrays (7).
Functional linkages computed for some 68 genomes are available
on the web at
http://169.232.137.207/cgi-dev/functionator/pronav/.
Soon results will be available for more than 150 fully
sequenced genomes.
In an application of functional linkages to structural
genomics, we have identified pairs of proteins encoded by
the genome of Mycobacterium tuberculosis that are likely
to be linked (8). A pair of these which did not express
individually was found to express well when encoded on
the same plasmid, and to form a complex, and to
crystallize. We are considering ways to scale up this
procedure to a medium-throughput process.
References
| 1. |
"Protein Function in the Post-Genomic Era" Eisenberg, D., Marcotte, E.M., Xenarios, I., and Yeates, T. Nature, 405, 823-826 (2000). |
| 2. |
"Prolinks: a database of protein functional linkages derived from coevolution." Bowers, P. M. et al. Genome Biol 5, R35 (2004). |
| 3. |
"Inference of protein function and protein linkages in M. tuberculosis based on prokaryotic genome organization: a combined computational approach" Strong, M., Mallick, P., Pellegrini, M., Thompson, M. J., Eisenberg, D., Genome Biology, 4:R59, 2-16, (2003). |
| 4. |
"Detecting Protein Function and Protein-Protein Interactions from Genome Sequences" Marcotte, E., Pellegrini, M., Ng, H.-L., Rice, D.W., Yeates, T.O., and Eisenberg, D., Science, 285, 751-753 (1999). |
| 5. |
"Assigning Protein Functions by Comparative Genome Analysis: Protein Phylogenetic Profiles" Pellegrini, M., Marcotte, E.M., Thompson, M.J., Eisenberg, D., and Yeates, T.O. PNAS USA, 96, 4285-4288 (1999). |
| 6. |
"Inference of protein function and protein linkages in M. tuberculosis based on prokaryotic genome organization: a combined computational approach" Strong, M., Mallick, P., Pellegrini, M., Thompson, M. J., Eisenberg, D., Genome Biology, 4:R59, 2-16, (2003). |
| 7. |
"A Combined Algorithm for Genome-wide Prediction of Protein Function" Marcotte, E.M., Pellegrini, M., Thompson, M.J., Yeates, T.O., and Eisenberg, D., Nature, 402, 83-86 (1999). |
| 8. |
"Visualization and Interpretation of Protein Networks in Mycobacterium tuberculosis Based on Hierarchical Clustering of Genome-Wide Functional Linkage Maps." Strong, M., Graeber, T. G., Beeby, M., Pellegrini, M., Thompson, M. J., Yeates, T. O., Eisenberg, D., Nucleic Acids Research, (2003). |
|
|
| |
|
|
