DOI: 10.1126/science.1092645. Structure-Based Assembly of Protein Complexes in Yeast

Structure-Based Assembly of Protein Complexes in Yeast

10.1126/science.1092645

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

Images of entire cells are preceding atomic structures of the separate molecular machines that they contain. The resulting gap in knowledge can be partly bridged by protein-protein interactions, bioinformatics, and electron microscopy. Here we use interactions of known three-dimensional structure to model a large set of yeast complexes, which we also screen by electron microscopy. For 54 of 102 complexes, we obtain at least partial models of interacting subunits. For 29, including the exosome, the chaperonin containing TCP-1, a 3′-messenger RNA degradation complex, and RNA polymerase II, the process suggests atomic details not easily seen by homology, involving the combination of two or more known structures. We also consider interactions between complexes (cross-talk) and use these to construct a structure-based network of molecular machines in the cell.

Bibliography

Aloy, P., BoÌttcher, B., Ceulemans, H., Leutwein, C., Mellwig, C., Fischer, S., Gavin, A.-C., Bork, P., Superti-Furga, G., Serrano, L., & Russell, R. B. (2004). Structure-Based Assembly of Protein Complexes in Yeast. Science, 303(5666), 2026â2029.

Authors 11

Patrick Aloy (first)
Bettina Böttcher (additional)
Hugo Ceulemans (additional)
Christina Leutwein (additional)
Christian Mellwig (additional)
Susanne Fischer (additional)
Anne-Claude Gavin (additional)
Peer Bork (additional)
Giulio Superti-Furga (additional)
Luis Serrano (additional)
Robert B. Russell (additional)

References 33 Referenced 315

10.1016/S1097-2765(00)80023-4
10.1126/science.1076184
10.1126/science.289.5481.905
C. L. Poglitschet al., Cell98, 791 (1999). (10.1016/S0092-8674(00)81513-5) / Cell (1999)
10.1038/35001009
10.1038/415141a
Materials and methods are available as supporting material on Science Online.
L. Lo Conte, S. E. Brenner, T. J. Hubbard, C. Chothia, A. G. Murzin, Nucleic Acids Res.30, 264 (2002). (10.1093/nar/30.1.264) / Nucleic Acids Res. (2002)
P. Aloy, H. Ceulemans, A. Stark, R. B. Russell, J. Mol. Biol.332, 989 (2003). (10.1016/j.jmb.2003.07.006) / J. Mol. Biol. (2003)
10.1093/nar/30.1.31
H. Ceulemans R. B. Russell J. Mol. Biol. in press.
P. D. Jeffrey, L. Tong, N. P. Pavletich, Genes Dev.14, 3115 (2000). (10.1101/gad.851100) / Genes Dev. (2000)
P. Aloy, R. B. Russell, Proc. Natl. Acad. Sci. U.S.A.99, 5896 (2002). (10.1073/pnas.092147999) / Proc. Natl. Acad. Sci. U.S.A. (2002)
10.1016/S1097-2765(02)00749-9
J. Janinet al., Proteins52, 2 (2003). (10.1002/prot.10381) / Proteins (2003)
P. Aloyet al., EMBO Rep.3, 628 (2002). (10.1093/embo-reports/kvf135) / EMBO Rep. (2002)
M. F. Symmons, G. H. Jones, B. F. Luisi, Struct. Fold Des.8, 1215 (2000). (10.1016/S0969-2126(00)00521-9) / Struct. Fold Des. (2000)
D. A. Bushnell, R. D. Kornberg, Proc. Natl. Acad. Sci. U.S.A.100, 6969 (2003). (10.1073/pnas.1130601100) / Proc. Natl. Acad. Sci. U.S.A. (2003)
10.1016/S0092-8674(02)00655-4
J. M. Valpuesta, J. Martin-Benito, P. Gomez-Puertas, J. L. Carrascosa, K. R. Willison, FEBS Lett.529, 11 (2002). (10.1016/S0014-5793(02)03180-0) / FEBS Lett. (2002)
J. N. McLaughlinet al., Proc. Natl. Acad. Sci. U.S.A.99, 7962 (2002). (10.1073/pnas.112075699) / Proc. Natl. Acad. Sci. U.S.A. (2002)
L. Ditzelet al., Cell93, 125 (1998). (10.1016/S0092-8674(00)81152-6) / Cell (1998)
R. Gaudet, J. R. Savage, J. N. McLaughlin, B. M. Willardson, P. B. Sigler, Mol. Cell3, 649 (1999). (10.1016/S1097-2765(00)80358-5) / Mol. Cell (1999)
J. R. Chamberlain, Y. Lee, W. S. Lane, D. R. Engelke, Genes Dev.12, 1678 (1998). (10.1101/gad.12.11.1678) / Genes Dev. (1998)
J. T. Brown, X. Bai, A. W. Johnson, RNA6, 449 (2000). (10.1017/S1355838200991787) / RNA (2000)
P. Aloy, R. B. Russell, Trends Biochem. Sci.27, 633 (2002). (10.1016/S0968-0004(02)02204-1) / Trends Biochem. Sci. (2002)
A. C. Gavin, G. Superti-Furga, Curr. Opin. Chem. Biol.7, 21 (2003). (10.1016/S1367-5931(02)00007-8) / Curr. Opin. Chem. Biol. (2003)
10.1126/science.1065103
S. Tan, Y. Hunziker, D. F. Sargent, T. J. Richmond, Nature381, 127 (1996). (10.1038/381127a0) / Nature (1996)
F. T. Tsai, P. B. Sigler, EMBO J.19, 25 (2000). (10.1093/emboj/19.1.25) / EMBO J. (2000)
10.1073/pnas.111145798
A. Sali, R. Glaeser, T. Earnest, W. Baumeister, Nature422, 216 (2003). (10.1038/nature01513) / Nature (2003)
We thank A. Musacchio (European Institute of Oncology Italy) for the functional classification of complexes and K. Leonard and E. Conti (EMBL) for help during the EM screen.

Dates

Type	When
Created	21 years, 4 months ago (March 25, 2004, 4:33 p.m.)
Deposited	1 year, 7 months ago (Jan. 9, 2024, 11:04 p.m.)
Indexed	2 days, 1 hour ago (Aug. 19, 2025, 6:26 a.m.)
Issued	21 years, 4 months ago (March 26, 2004)
Published	21 years, 4 months ago (March 26, 2004)
Published Print	21 years, 4 months ago (March 26, 2004)

Funders 0

None

BibTeX

@article{Aloy_2004, title={Structure-Based Assembly of Protein Complexes in Yeast}, volume={303}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1092645}, DOI={10.1126/science.1092645}, number={5666}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Aloy, Patrick and Böttcher, Bettina and Ceulemans, Hugo and Leutwein, Christina and Mellwig, Christian and Fischer, Susanne and Gavin, Anne-Claude and Bork, Peer and Superti-Furga, Giulio and Serrano, Luis and Russell, Robert B.}, year={2004}, month=mar, pages={2026–2029} }

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