# Richard Brimacombe

Richard Brimacombe is a molecular biologist known for experimentally determining the secondary and three-dimensional structure of ribosomal RNA (rRNA) in the [Escherichia coli](https://www.edgepedia.org/escherichia-coli) ribosome, working for most of his career at the Max-Planck-Institut für molekulare Genetik in Berlin.<sup>[1](https://gepris.dfg.de/person/1013925)</sup> His Nature publications on rRNA included a 1978 Scientific Correspondence on the sequence of E. coli 16S ribosomal RNA<sup>[2](https://www.nature.com/articles/276445a0)</sup> and a 1981 commentary on its secondary structure and evolution,<sup>[3](https://doi.org/10.1038/294209a0)</sup> and his research group spent roughly fifteen years mapping which RNA and protein sequences physically touch inside the ribosomal subunits.<sup>[4](https://doi.org/10.1016/0300-9084(91)90134-m)</sup> 

| Fact | Detail |
|---|---|
| Field | Molecular biology; structure of ribosomal RNA and RNA-protein interactions in the E. coli ribosome |
| Main institution | Max-Planck-Institut für molekulare Genetik, Ihnestraße 63-73, 14195 Berlin<sup>[1](https://gepris.dfg.de/person/1013925)</sup> |
| Berlin career start | Joined the department at the MPIMG at the end of 1973<sup>[4](https://doi.org/10.1016/0300-9084(91)90134-m)</sup> |
| Signature work | A detailed three-dimensional model of E. coli 16S rRNA in situ in the 30S subunit, Journal of Molecular Biology, 1988<sup>[5](https://doi.org/10.1016/0022-2836(88)90383-x)</sup> |
| DFG funding | Two completed projects, 1999–2002 and 2001–2004, on the bacterial ribosome approaching atomic resolution<sup>[6](https://gepris.dfg.de/project/5224816)</sup> |
| Methods | Intra-RNA and RNA-protein cross-linking, two-dimensional gel electrophoresis, modeling against electron-microscopic maps<sup>[4](https://doi.org/10.1016/0300-9084(91)90134-m)</sup> |
| Latest dated review | Bacterial ribosome structure approaching atomic resolution, 2009<sup>[7](https://pubmed.ncbi.nlm.nih.gov/19649891)</sup> |

## Career at the Max Planck Institute

According to a 1991 review in *Biochimie*, Brimacombe joined the department at the Max-Planck-Institut für molekulare Genetik at the end of 1973, and there took up an RNA-protein cross-linking approach to the E. coli ribosome that grew to become the major field of investigation in his research group for the following fifteen to sixteen years.<sup>[4](https://doi.org/10.1016/0300-9084(91)90134-m)</sup> His early Berlin publications include a Nature Scientific Correspondence on the sequence of E. coli 16S ribosomal RNA in the issue dated 30 November 1978, signed from the institute's department in Berlin-Dahlem.<sup>[2](https://www.nature.com/articles/276445a0)</sup>

The cross-linking project was, by his own account in 1991, just recently concluded at that point, and his later work shifted to assembling the accumulated interaction data into complete three-dimensional models of the rRNA.<sup>[4](https://doi.org/10.1016/0300-9084(91)90134-m)</sup> In June 1999 he presented the resulting 13 Å-resolution structure of bacterial ribosomal RNA at a Biochemical Society meeting, still from the Berlin institute.<sup>[8](https://doi.org/10.1042/bst027a089)</sup> The German Research Foundation (DFG) funded a couple of his projects in this period, according to its GEPRIS records: Die dreidimensionale Struktur des bakteriellen Ribosoms: der Übergang zu atomarer Auflösung, running from 1999 to 2002, and Strukturelle und funktionelle Untersuchungen des Escherichia coli Ribosoms bei "quasi atomarer" Auflösung, from 2001 to 2004; both are recorded as completed, with none running since.<sup>[1](https://gepris.dfg.de/person/1013925)</sup><sup> • </sup><sup>[6](https://gepris.dfg.de/project/5224816)</sup> 

## Representative work

The 1988 Journal of Molecular Biology paper A detailed model of the three-dimensional structure of Escherichia coli 16S ribosomal RNA in situ in the 30S subunit ([DOI](https://doi.org/10.1016/0022-2836(88)90383-x))<sup>[5](https://doi.org/10.1016/0022-2836(88)90383-x)</sup> stands for the mature phase of his program: it converted years of cross-linking and topographical data into an explicit three-dimensional folding of the entire 16S rRNA inside the small ribosomal subunit, correlating RNA structure with the arrangement of the ribosomal proteins known from neutron scattering, immuno-electron microscopy, and protein-protein cross-linking.<sup>[4](https://doi.org/10.1016/0300-9084(91)90134-m)</sup>

## Experimental maps versus comparative models

Brimacombe's secondary-structure work proceeded from direct experiment. In a 1980 Nucleic Acids Research study, ribonucleoprotein fragments were isolated by mild ribonuclease digestion of E. coli 30S subunits, deproteinized, and partially redigested; interacting fragments, identified as pairs or families by two-dimensional gel electrophoresis, yielded an experimental secondary-structure model for 16S rRNA covering about 80% of the molecule.<sup>[9](https://doi.org/10.1093/nar/8.11.2377)</sup> That model agreed very substantially with the comparative structure proposed the same way from phylogenetic sequence comparison, which also covered about 80% of the RNA, though areas of discrepancy remained, and the experimental data gave evidence for multiple alternative structures supporting proposed ribosomal "switches".<sup>[9](https://doi.org/10.1093/nar/8.11.2377)</sup>

The companion 1981 study extended the approach to the large subunit: short base-paired fragments and fragments containing intra-RNA cross-links were isolated from E. coli 23S rRNA and 50S subunits by two-dimensional gel electrophoresis, and the resulting model, refined against chloroplast and mitochondrial rDNA sequences, was organized in well-defined domains with over 450 compensating base changes between the compared species and included structural switches, one involving 5S rRNA, according to the study in *Nucleic Acids Research*.<sup>[10](https://doi.org/10.1093/nar/9.14.3287)</sup> His commentary "Secondary structure and evolution of ribosomal RNA" appeared in Nature 294, pages 209 to 210, in the issue dated 19 November 1981.<sup>[3](https://doi.org/10.1038/294209a0)</sup>

By 1991, three essentially similar secondary-structure models existed for each of the 16S and 23S molecules, derived by a two-track approach combining experimental data from E. coli RNA with phylogenetic comparison, and the latest versions had converged to the point of being identical in all but a few areas.<sup>[11](https://doi.org/10.1042/bj2290001)</sup> On the cross-linking side, the early studies had identified only secondary structural cross-links, but later partial-digestion conditions localized tertiary as well as secondary intra-RNA cross-links in both 50S and 30S subunits, moving the technique from planar folding maps to genuine long-range contacts.<sup>[11](https://doi.org/10.1042/bj2290001)</sup>

The 1995 European Journal of Biochemistry review "The Structure of Ribosomal RNA: A Three-Dimensional Jigsaw Puzzle" drew this together, covering site-directed cross-linking to tRNA, mRNA, and the growing peptide chain, topographical data for the complete 16S and 23S molecules, and a new 16S RNA model, alongside open problems such as the 530 loop controversy and uncertainties in fitting the 16S RNA to the 30S protein distribution.<sup>[12](https://doi.org/10.1111/j.1432-1033.1995.tb20572.x)</sup> A November 1994 Science News report, "Piecing Together the Ribosome", described how this Berlin biochemist had presented computer renditions of the ribosome, the cell's protein-producing machine, to a molecular biology meeting that August.<sup>[13](https://doi.org/10.2307/3978543)</sup> 

## The atomic-resolution era

His DFG project of 1999 to 2002 stated the strategy plainly: to combine biochemically derived three-dimensional models of the ribosome with electron-microscopy reconstructions, building on a first complete 3D model of all the rRNA, meaning the 5S, 16S, and 23S molecules, fitted to a 13 Å EM reconstruction.<sup>[6](https://gepris.dfg.de/project/5224816)</sup> The project abstract records that atomic structures of the 30S subunit from [Thermus thermophilus](https://www.edgepedia.org/thermus-thermophilus) and the 50S subunit from Haloarcula marismortui were published during 2000, and notes that these ribosomes differ substantially from that of E. coli.<sup>[6](https://gepris.dfg.de/project/5224816)</sup> His review "The Bacterial Ribosome at Atomic Resolution" placed the isolation and detailed analysis of intra-RNA cross-links induced in ribosomal subunits in the context of these emerging atomic-resolution structures.<sup>[14](https://doi.org/10.1016/s0969-2126(00)00510-4)</sup>

A 2009 review, "Bacterial ribosome structure: approaching atomic resolution", assessed the field at that transition: [X-ray crystallography](https://www.edgepedia.org/x-ray-crystallography) had by then produced near-complete atomic structures for both the 16S and 23S rRNA molecules from thermophilic and halophilic ribosomes, while cryo-electron microscopic studies of E. coli ribosomes in various functional states were yielding structures at single-figure resolution and still improving.<sup>[7](https://pubmed.ncbi.nlm.nih.gov/19649891)</sup> His earlier review of the emerging three-dimensional structure and function of 16S rRNA, published in [Biochemistry](https://www.edgepedia.org/biochemistry) in 1988, marks the midpoint between the first cross-linking maps and these later syntheses.<sup>[15](https://doi.org/10.1021/bi00412a001)</sup>

## References


1. [DFG GEPRIS person record 1013925, Richard Brimacombe Ph.D.](https://gepris.dfg.de/person/1013925)
2. [Brimacombe, R. The sequence of E. coli 16S ribosomal RNA. Nature 276, 445 (1978)](https://www.nature.com/articles/276445a0)
3. [Brimacombe, R. Secondary structure and evolution of ribosomal RNA. Nature 294, 209–210 (1981)](https://doi.org/10.1038/294209a0)
4. https://doi.org/10.1016/0300-9084(91)90134-m
5. https://doi.org/10.1016/0022-2836(88)90383-x
6. [DFG GEPRIS project 5224816, Die dreidimensionale Struktur des bakteriellen Ribosoms: der Übergang zu atomarer Auflösung](https://gepris.dfg.de/project/5224816)
7. [Brimacombe, R. Bacterial ribosome structure: approaching atomic resolution (2009), PubMed record](https://pubmed.ncbi.nlm.nih.gov/19649891)
8. [Brimacombe, R. The Three-Dimensional Structure of Bacterial Ribosomal RNA at 13 Å Resolution. Biochem Soc Trans 27(3): A89 (1999)](https://doi.org/10.1042/bst027a089)
9. [Glotz and Brimacombe. An experimentally-derived model for the secondary structure of the 16S ribosomal RNA from Escherichia coli. Nucleic Acids Research (1980)](https://doi.org/10.1093/nar/8.11.2377)
10. [Secondary structure of the large subunit ribosomal RNA from Escherichia coli, Zea mays chloroplast, and human and mouse mitochondrial ribosomes. Nucleic Acids Research (1981)](https://doi.org/10.1093/nar/9.14.3287)
11. [Structure and function of ribosomal RNA. Biochemical Journal (1991)](https://doi.org/10.1042/bj2290001)
12. [Brimacombe, R. The Structure of Ribosomal RNA: A Three-Dimensional Jigsaw Puzzle. European Journal of Biochemistry (1995)](https://doi.org/10.1111/j.1432-1033.1995.tb20572.x)
13. [Piecing Together the Ribosome. Science News (5 November 1994)](https://doi.org/10.2307/3978543)
14. https://doi.org/10.1016/s0969-2126(00)00510-4
15. [Brimacombe, R. The emerging three-dimensional structure and function of 16S ribosomal RNA. Biochemistry 27, 4207–4214 (1988)](https://doi.org/10.1021/bi00412a001)



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*Topic: Encyclopedia › Life and health › Life and health scientists › Life scientists › Researchers in structural biology, biochemistry, and biophysics › Translation and ribosome structure*

*Initially written Sep 21, 2026 · Reviewed: Sep 25, 2026 · Edited: Sep 25, 2026 · Last review: Sep 25, 2026*

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