Dieter Oesterhelt (1940–2022): Life with light and color, pioneer of membrane protein research

Dieter Oesterhelt (simply called “Oe” by his coworkers) (Figure 1) died on Nov. 28^th 2022 in Munich, shortly after his 82^nd birthday. Dieter was widely known and deeply respected as the discoverer of bacteriorhodopsin, BR, the first known microbial rhodopsin, which– in large part due to his work – became understood at the level of an archetypal membrane protein. Dieter made countless contributions: to the understanding of BR and many other membrane proteins, to the development of biophysical techniques that were later used to study multiple members of the microbial rhodopsin family, and to insights into many other membrane proteins with completely different functions.

Figure 1 

A photograph of Dr. Dieter Oesterhelt

Although at present and likely far into the future, it is the applications of microbial light-driven pumps, channels, and enzymes for optogenetics that represent the greatest broad impact deriving from his work, Dieter’s original discovery of the color and function of the so-called purple membrane from the halophilic archaeon Halobacterium salinarum (formerly halobium) – and the remarkable availability, simplicity, and stability of its single protein bacteriorhodopsin– laid the foundations for the broad membrane-protein research field that he launched in 1971.

Born in 1940 in Munich, his home town and major workplace, Dieter studied chemistry at the local Ludwig-Maximilian-University, graduated in 1965 and worked with the Nobel Laureate Feodor Lynen on the structure of fatty acid synthetase [1]. Since the crystals he obtained were– disappointingly– disordered, he joined the laboratory of Walter Stoeckenius in San Francisco in 1969 to use electron microscopy. In this lab he met Allen Blaurock who worked on purple colored membrane patches from H. salinarum. Dieter started the biochemical characterization of this strange membrane as a side project, discovered that it contains only one single protein, and showed that its color is caused by the cofactor retinal (vitamin-A-aldehyde) just as in animal rhodopsins. For that reason he named the chromoprotein bacteriorhodopsin [2].

Back in Munich, Dieter found that illumination bleached the purple color reversibly, just as the color change of rhodopsin in animal eyes (including those of human beings) upon illumination. But the color of BR instead regenerated rapidly and did not require enzymatic reactions. In 1972 Dieter proposed that BR functions as a light-driven proton pump that energizes the halobacteria by creating an electrochemical proton gradient across the cytoplasmic membrane, which is used to drive the synthesis of ATP [3]. This concept was compatible with Peter Mitchell’s chemiosmotic theory– and indeed essential to the final acceptance of the chemiosmotic principle. Dieter was appointed to a group leader position at the Friedrich Miescher Laboratory in Tübingen in 1973. Only two year later he accepted a full professorship at Würzburg University and shortly thereafter he was appointed as a director at the Max Planck Institute for Biochemistry in Martinsried (near Munich) where he worked from 1979 until his retirement in 2008. In this position, with substantial resources newly available, Dieter carefully characterized the bioenergetic functionality of BR, studied its reconstitution from the apoproteins via several clearly defined intermediate steps, and analyzed the dynamics of the light-triggered proton-pumping reaction cycle. Here it is important for us to keep in mind, from our vantage point in history, that in the 1970s no membrane protein sequence, no gene sequence, and no structural information about any membrane protein was available.

In 1978, a sudden and enormously enlightening moment came to pass for Dieter and the new BR field, when Gobind Khorana from MIT (who had decided to switch from working on nucleotide chemistry to working on membrane proteins), and in parallel, Yuri Ovchinnikov of the Shemyakin Institute in Moscow, published independently the amino acid sequence of BR (representing the first known sequence of a membrane protein) [4,5]. Khorana further contributed the BR gene sequence two years later [6]. These two findings triggered a long process of molecular characterization of BR, with Dieter and Gobind as leaders of a prospering field operating at the highest scientific level, in an extremely fruitful and friendly competition characterized by deep mutual respect. Both labs, with their many collaborators, elucidated the molecular properties and constraints that determine BR color, photodynamics over 15 log units in time (from femtoseconds to tens of seconds) after photoexcitation, and the constituent amino acids guiding proton movement up the electrochemical gradient through spatially separated and alternating proton cages which prevent back-flow, all culminating in Dieter’s IST-model [7]. Whereas Khorana’s work was based on mutated BR-variants expressed in E. coli [8], Dieter relied on BR-variants generated in the original halobacterial host [9,10].

In this setting, Dieter conducted in conjunction with his many collaborators pioneering work on a number of technologies that were later widely used for the many molecular studies. Among these were the 2D and 3D BR-structure determination with R. Henderson [11–13], ultra-fast spectroscopy with W. Kaiser [14,15], analysis of protein dynamics by time resolved FTIR spectroscopy with Klaus Gerwert [16], Raman Spectroscopy with W. Stockburger [17–19], and NMR with M. Engelhard and H. Oschkinat [20,21]. The technology and molecular approaches that were developed for and with BR laid the groundwork for the rapid characterization of countless other microbial rhodopsins including the chloride pump halorhodopsin [22], the sensory rhodopsins SRI and SRII, and the channelrhodopsins in Dieter’s and others’ laboratories.

Dieter also made many important contributions to other fields. For example, he discovered a plant ferredoxin in halobacteria, representing one of the earliest-known cases of horizontal gene transfer [23]. He also showed in collaboration with W. Kaiser and W. Zinth that the accessory chlorophyll of the photosynthetic reaction center is the first transient electron acceptor of the electron released by the special pair after photoexcitation [24]. With great enthusiasm, Dieter supported diverse and numerous technical BR applications, including biocomputing [25], holography [26], and pattern recognition. Dieter was a supporter of science in the broadest sense, and encouraged a number of former students and coworkers to launch independent research in his department; we gratefully acknowledge this generosity as beneficiaries. After bioenergetic studies on BR, and generation of the first 3D crystals that were at that time unsuitable for high-resolution structures, one of us (H.M.) switched to bacterial photosynthesis and crystallized the reaction centers of Rhodopseudomonas viridis which resulted in the first high-resolution structure of a membrane protein complex [27]. After working on halorhodopsin, P.H. studied the photobehaviour of the green alga Chlamydomonas [28], work that later resulted in the identification of the light-gated ion channel channelrhodopsin [29] now the most prominent optogenetic actuator.

The great success of Dieter’s department of membrane biochemistry arose from its creative atmosphere, where science came first but every individual personality was appreciated, respected, and supported. Dieter was also a very social person. He enjoyed lab parties and excursions, mostly to the mountains. He was a great runner, tennis player, downhill skier, and mountaineer, and enjoyed to be challenged by his group members.

Although Dieter was an enthusiastic experimentalist, he also was a highly active science administrator who served in numerous functions as science policy advisor, always seeking to identify the best science that could be supported by the available funds. Above all, he generously supported his colleagues as they made their transitions to independence.

For his pioneering science and his great scientific leadership Dieter Oesterhelt received many honors and awards, among them the Feldberg Award, Karl Heinz Beckurts-Award, Cross of Merit of the German Republic, the Mendel-Medaille of the Leopoldina, the Otto Warburg Medaille of the German Society for Biochemistry and Molecular Biology (GBM), the Otto-Hahn Award for Chemistry and Physics, the Werner von Siemens-Ring, the Bavarian Maximilian Order, and recently he shared the Lasker Award for Basic Science (2021) with P.H. and Karl Deisseroth.

Many of his collaborators and trainees around the world have lost a deeply respected and trusted advisor, supervisor and friend, who respected strengths and weaknesses but always pushed his colleagues forward into unexplored territories. Dieter left behind his wife Holmrike and from his first marriage his three children Patrick, Filipp and Verena, and four grandchildren.

Beyond those who knew him, the global scientific community as a whole has lost a great scientist and visionary leader. We all owe him a great deal, and will continue to honor his memory in our work.

Finally, Dieter organized the 1^st “International Conference on Retinal Proteins” in 1984 on Ringberg Castle in Bavaria, Germany.

Acknowledgements

We are grateful for discussion and support in the writing of this tribute from Dieters – and our– friends and colleagues Richard Henderson (Cambridge) and Karl Deisseroth (Stanford).

References

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