Axel T. Brunger: Difference between revisions
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== Academic career == |
== Academic career == |
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Brunger held a NATO postdoctoral fellowship to work with [[Martin Karplus]] at [[Harvard University]], where he subsequently became a research associate in the Department of Chemistry after a brief return to Germany.<ref name="nas" /> He joined the Molecular Biophysics and Biochemistry department at [[Yale University]] in 1987 and moved to [[Stanford University]] in 2000. |
Brunger held a NATO postdoctoral fellowship to work with [[Martin Karplus]] at [[Harvard University]], where he subsequently became a research associate in the Department of Chemistry after a brief return to Germany.<ref name="nas" /> He joined the Molecular Biophysics and Biochemistry department at [[Yale University]] in 1987 and moved to [[Stanford University]] in 2000.<ref name="stanford" /> Brunger was elected to the [[United States National Academy of Sciences]] in 2005<ref name="stanford" /> and won the inaugural [[DeLano Award for Computational Biosciences]] in 2011.<ref name=delano>{{cite web|title=Axel T. Brunger wins inaugural ASBMB DeLano Award|url=http://www.asbmb.org/asbmbtoday/asbmbtoday_article.aspx?id=11372&terms=axel|accessdate=22 January 2015}}</ref> |
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the American Academy of Arts & Sciences. |
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== Research == |
== Research == |
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Brunger is known for developing a computer program called [[X-PLOR]],<ref>{{cite journal|last1= |
Brunger is known for developing a computer program called [[Crystallography and NMR system|CNS]] used for solving structures based on [[X-ray crystallography|X-ray diffraction]] or [[protein NMR|solution NMR]] data, which was first released in 1992. The program is a major extension of a 1987 program developed with [[John Kuriyan]] and Karplus called [[X-PLOR]],<ref>{{cite journal|last1=Brünger|first1=AT|last2=Kuriyan|first2=J|last3=Karplus|first3=M|title=Crystallographic R factor refinement by molecular dynamics.|journal=Science|date=23 January 1987|volume=235|issue=4787|pages=458–60|pmid=17810339|bibcode = 1987Sci...235..458B |doi = 10.1126/science.235.4787.458 |s2cid=38261757}}</ref> whose original inspiration was motivated by [[Marius Clore]]'s efforts in interpreting NMR data and which has been extended by Clore's continued development of [[XPLOR-NIH]].<ref name="nas" /> |
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Brunger introduced the RFree technique to cross-validate the model given the observed data.<ref name=Rfree>{{cite journal |author=Brunger AT |year=1992 |title=Free R value: a novel statistical quantity for assessing the accuracy of crystal structures |journal=Nature |volume=355 |pages=472–475 |doi=10.1038/355472a0|bibcode = 1992Natur.355..472B |pmid=18481394 |issue=6359|s2cid=2462215 |author-link=Axel Brunger }}</ref> |
These programs make use of a method called [[simulated annealing]] in conjunction with [[molecular dynamics]] to refine protein structures. X-PLOR was the first time a modern optimization technique was applied to the problem of crystallographic refinement. Brunger also subsequently introduced the RFree technique to cross-validate the model given the observed data.<ref name=Rfree>{{cite journal |author=Brunger AT |year=1992 |title=Free R value: a novel statistical quantity for assessing the accuracy of crystal structures |journal=Nature |volume=355 |pages=472–475 |doi=10.1038/355472a0|bibcode = 1992Natur.355..472B |pmid=18481394 |issue=6359|s2cid=2462215 |author-link=Axel Brunger }}</ref> In the mid-1990s, his team extended X-PLOR into a complete system to solve structures, which then became the more full-featured tool [[Crystallography and NMR system|CNS]], capable of performing a series of steps necessary for crystallography structure determination, such as obtaining phases from experimental data and [[molecular replacement]] phasing from known homologous structures.<ref>{{cite journal|last1=Brünger|first1=AT|last2=Adams|first2=PD|last3=Clore|first3=GM|last4=DeLano|first4=WL|last5=Gros|first5=P|last6=Grosse-Kunstleve|first6=RW|last7=Jiang|first7=JS|last8=Kuszewski|first8=J|last9=Nilges|first9=M|last10=Pannu|first10=NS|last11=Read|first11=RJ|last12=Rice|first12=LM|last13=Simonson|first13=T|last14=Warren|first14=GL|title=Crystallography & NMR system: A new software suite for macromolecular structure determination.|journal=Acta Crystallographica Section D|date=1 September 1998|volume=54|issue=Pt 5|pages=905–21|pmid=9757107|doi=10.1107/s0907444998003254}}</ref> |
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Brunger's research group currently studies the molecular mechanism of [[synaptic vesicle]] fusion in [[neurotransmission]].<ref name="stanford" /> |
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Since the mid-1990s, Brunger has applied his expertise in structural biology to study the molecular mechanisms of synaptic proteins that enable nerve cell communication by [[neurotransmission]]. At the time, scientists knew that the SNARE protein complex involved in neurotransmission consisted of synaptobrevin, syntaxin-1, and SNAP-25. Synaptic vesicles carry synaptobrevin, along with neurotransmitters, to the nerve |
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cell membrane’s inner face, which contains syntaxin and SNAP-25. As the respective SNAREs zip up, they fuse the synaptic vesicle membrane and the nerve cell membrane, releasing neurotransmitter from the pre-synaptic neuron. In 1998, Brunger and coworkers <ref>{{cite journal|last1=Sutton|first1=RB|last2=Fasshauer|first2=D|last3=Jahn|first3=R|last4=Brunger|first4=AT|title=Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 A resolution.|journal=Nature|date=24 September 1998|volume=395|pages=347–53|doi = 10.1038/26412 }}</ref> showed that the corkscrew-shaped SNARE proteins assemble into quartets of one syntaxin-1, one synaptobrevin, and two SNAP-25 helices (collaboration with Reinhard Jahn). The proteins all lie in parallel, with their heads pointing in the same direction, to promote membrane fusion. |
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Since moving to Stanford University in 2000, Brunger developed a reconstituted system that enables them to study synaptic fusion at greater level of detail than possible in live neurons. The team studied the molecular mechanism of neuronal SNAREs, complexin, and synaptotagmin, as well as other factors involved in priming and pre-synaptic plasticity. In 2015 and 2018, Brunger’s team used single particle electron cryo-microscopy to determine structures of the supercomplex of SNAREs, the ATPase NSF, and the adapter protein α-SNAP <ref>{{cite journal|last1=Zhao|first1=M|last2=Wu|first2=S|last3=Zhou|first3=Q|last4=Vivona|first4=S|last5=Cipriano|first5=DJ|last6=Cheng|first6=Y|last7=Brunger|first7=AT|title=Mechanistic insights into the recycling machine of the SNARE complex.|journal=Nature|date=5 February 2015|volume=518|pages=61-67|doi = 10.1038/nature14148 }}</ref>. These structures, along with functional studies, revealed first glimpses of the molecular mechanism of NSF-mediated SNARE complex disassembly, which allows SNARE to be recycled for the next round of synaptic vesicle fusion. In 2015 and 2017, Brunger’s team determined atomic-resolution structures of complexes of the |
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calcium sensor synaptotagmin-1, the neuronal SNARE complex, and the regulator complexin. These structures suggested an unlocking mechanism that is triggered by calcium binding to the synaptotagmin molecules, leading to SNARE complex zippering and membrane fusion. |
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== References == |
== References == |
Revision as of 15:06, 22 August 2022
Axel T. Brunger | |
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Born | Leipzig, Germany | November 25, 1956
Education | |
Known for | Developing Crystallography and NMR system |
Scientific career | |
Institutions |
Axel T. Brunger (born November 25, 1956) is a German American biophysicist. He is Professor of Molecular and Cellular Physiology, and Neurology, of Photon Science and, by courtesy, of Structural Biology at Stanford University, and a Howard Hughes Medical Institute Investigator.[1] He served as the Chair of the Department of Molecular and Cellular Physiology (2013–2017).
Early life
Brunger was born in Leipzig, Germany, on November 25, 1956. He graduated with a degree in Physics and Mathematics from the University of Hamburg in 1977. He completed his Diplom in Physics from the University of Hamburg in 1980. He completed his PhD in Biophysics from Technical University of Munich in 1982, advised by Klaus Schulten.[2]
Academic career
Brunger held a NATO postdoctoral fellowship to work with Martin Karplus at Harvard University, where he subsequently became a research associate in the Department of Chemistry after a brief return to Germany.[2] He joined the Molecular Biophysics and Biochemistry department at Yale University in 1987 and moved to Stanford University in 2000.[1] Brunger was elected to the United States National Academy of Sciences in 2005[1] and won the inaugural DeLano Award for Computational Biosciences in 2011.[3]
Research
Brunger is known for developing a computer program called CNS used for solving structures based on X-ray diffraction or solution NMR data, which was first released in 1992. The program is a major extension of a 1987 program developed with John Kuriyan and Karplus called X-PLOR,[4] whose original inspiration was motivated by Marius Clore's efforts in interpreting NMR data and which has been extended by Clore's continued development of XPLOR-NIH.[2]
These programs make use of a method called simulated annealing in conjunction with molecular dynamics to refine protein structures. X-PLOR was the first time a modern optimization technique was applied to the problem of crystallographic refinement. Brunger also subsequently introduced the RFree technique to cross-validate the model given the observed data.[5] In the mid-1990s, his team extended X-PLOR into a complete system to solve structures, which then became the more full-featured tool CNS, capable of performing a series of steps necessary for crystallography structure determination, such as obtaining phases from experimental data and molecular replacement phasing from known homologous structures.[6]
Brunger's research group currently studies the molecular mechanism of synaptic vesicle fusion in neurotransmission.[1]
References
- ^ a b c d "Axel Brunger". Stanford School of Medicine. Retrieved 14 March 2015.
- ^ a b c Mossman, K. (30 July 2008). "Profile of Axel Brunger". Proceedings of the National Academy of Sciences. 105 (31): 10643–10645. Bibcode:2008PNAS..10510643M. doi:10.1073/pnas.0806286105. PMC 2504785. PMID 18667701.
- ^ "Axel T. Brunger wins inaugural ASBMB DeLano Award". Retrieved 22 January 2015.
- ^ Brünger, AT; Kuriyan, J; Karplus, M (23 January 1987). "Crystallographic R factor refinement by molecular dynamics". Science. 235 (4787): 458–60. Bibcode:1987Sci...235..458B. doi:10.1126/science.235.4787.458. PMID 17810339. S2CID 38261757.
- ^ Brunger AT (1992). "Free R value: a novel statistical quantity for assessing the accuracy of crystal structures". Nature. 355 (6359): 472–475. Bibcode:1992Natur.355..472B. doi:10.1038/355472a0. PMID 18481394. S2CID 2462215.
- ^ Brünger, AT; Adams, PD; Clore, GM; DeLano, WL; Gros, P; Grosse-Kunstleve, RW; Jiang, JS; Kuszewski, J; Nilges, M; Pannu, NS; Read, RJ; Rice, LM; Simonson, T; Warren, GL (1 September 1998). "Crystallography & NMR system: A new software suite for macromolecular structure determination". Acta Crystallographica Section D. 54 (Pt 5): 905–21. doi:10.1107/s0907444998003254. PMID 9757107.
External links
- 1956 births
- 21st-century American physicists
- University of Hamburg alumni
- Technical University of Munich alumni
- German emigrants to the United States
- Harvard University staff
- Yale Department of Molecular Biophysics & Biochemistry faculty
- Living people
- Howard Hughes Medical Investigators
- Crystallographers
- Stanford University School of Medicine faculty
- Members of the United States National Academy of Sciences