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Kiyoshi Nagai

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This article is about the Japanese biologist. For the Japanese manga artist, see Go Nagai.
Kiyoshi Nagai
FRS
Kiyoshi Nagai, November 2018
Born(1949-06-25)June 25, 1949
Osaka, Japan
DiedSeptember 27, 2019(2019-09-27) (aged 70)
Cambridge, United Kingdom
NationalityJapanese
Alma materOsaka University (BSc, MSc, PhD)
Awards
Scientific career
InstitutionsMRC Laboratory of Molecular Biology
Thesis (1978)
Doctoral advisorHideki Morimoto
Websitewww2.mrc-lmb.cam.ac.uk/group-leaders/n-to-s/kiyoshi-nagai/

Kiyoshi Nagai FRS (June 25, 1949 – September 27, 2019) was a Japanese structural biologist at the MRC Laboratory of Molecular Biology Cambridge, UK. He was known for his work on the mechanism of RNA splicing and structures of the spliceosome.

Education

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Nagai studied at Osaka University and earned a Doctor of Philosophy under the supervision of Hideki Morimoto working on the allosteric effect in hemoglobin.[1]

Career and research

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In 1981 Nagai moved to the MRC Laboratory of Molecular Biology where he worked as a post-doc with Max Perutz on overproduction of eukaryotic proteins in E. coli.[1] He produced recombinant hemoglobin and studied its properties and evolution by crystallography and mutagenesis.[2][3] In 1987 he became a tenured group leader at the LMB and was joint head of the Division of Structural Studies from 2000 to 2010. He was appointed fellow of Darwin College, Cambridge in 1993.[4]

In 1990 his group solved the first structure of an RRM (RNA recognition motif) protein, U1A,[5] and in 1994 showed how it specifically binds RNA.[6] Subsequent work involved crystallographic studies of other components of the spliceosome, a large macromolecular machine that catalyses RNA splicing in eukaryotes, including components of the U2 snRNP[7] and the Sm proteins[8] and culminating in the crystal structures of the full U1 snRNP[9][10] and the U5 snRNP components Prp8[11] and Brr2.[12]

From 2014, Nagai's group used cryo-electron microscopy to study the spliceosome. Structures of the U5.U4/U6 tri-snRNP gave the first structural insights into the assembly of the spliceosome.[13][14] Nagai's subsequent structures of spliceosomes in various stages of assembly and catalysis[15][16] combined with structures from the groups of Reinhard Lührmann, Yigong Shi and others have provided crucial insight into the catalytic mechanism of pre-mRNA splicing.

Awards

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References

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  1. ^ a b Galej, Wojciech P.; Toor, Navtej; Newman, Andrew J.; Nagai, Kiyoshi (2018-04-25). "Molecular Mechanism and Evolution of Nuclear Pre-mRNA and Group II Intron Splicing: Insights from Cryo-Electron Microscopy Structures". Chemical Reviews. 118 (8): 4156–4176. doi:10.1021/acs.chemrev.7b00499. ISSN 1520-6890. PMID 29377672.
  2. ^ Nagai, K.; Thøgersen, H. C. (1984). "Generation of beta-globin by sequence-specific proteolysis of a hybrid protein produced in Escherichia coli". Nature. 309 (5971): 810–812. Bibcode:1984Natur.309..810N. doi:10.1038/309810a0. ISSN 0028-0836. PMID 6330564. S2CID 4307749.
  3. ^ Nagai, K.; Perutz, M. F.; Poyart, C. (1985). "Oxygen binding properties of human mutant hemoglobins synthesized in Escherichia coli". Proceedings of the National Academy of Sciences of the United States of America. 82 (21): 7252–7255. Bibcode:1985PNAS...82.7252N. doi:10.1073/pnas.82.21.7252. ISSN 0027-8424. PMC 390827. PMID 3903751.
  4. ^ "Master & fellows | www.darwin.cam.ac.uk". www.darwin.cam.ac.uk. Retrieved 2018-12-09.
  5. ^ Nagai, K.; Oubridge, C.; Jessen, T. H.; Li, J.; Evans, P. R. (1990-12-06). "Crystal structure of the RNA-binding domain of the U1 small nuclear ribonucleoprotein A". Nature. 348 (6301): 515–520. Bibcode:1990Natur.348..515N. doi:10.1038/348515a0. ISSN 0028-0836. PMID 2147232. S2CID 4336326.
  6. ^ Oubridge, C.; Ito, N.; Evans, P. R.; Teo, C. H.; Nagai, K. (1994-12-01). "Crystal structure at 1.92 A resolution of the RNA-binding domain of the U1A spliceosomal protein complexed with an RNA hairpin". Nature. 372 (6505): 432–438. Bibcode:1994Natur.372..432O. doi:10.1038/372432a0. ISSN 0028-0836. PMID 7984237. S2CID 9404488.
  7. ^ Price, S. R.; Evans, P. R.; Nagai, K. (1998-08-13). "Crystal structure of the spliceosomal U2B"-U2A' protein complex bound to a fragment of U2 small nuclear RNA". Nature. 394 (6694): 645–650. Bibcode:1998Natur.394..645P. doi:10.1038/29234. ISSN 0028-0836. PMID 9716128. S2CID 204999419.
  8. ^ Kambach, C.; Walke, S.; Young, R.; Avis, J. M.; de la Fortelle, E.; Raker, V. A.; Lührmann, R.; Li, J.; Nagai, K. (1999-02-05). "Crystal structures of two Sm protein complexes and their implications for the assembly of the spliceosomal snRNPs". Cell. 96 (3): 375–387. doi:10.1016/S0092-8674(00)80550-4. ISSN 0092-8674. PMID 10025403. S2CID 17379935.
  9. ^ Pomeranz Krummel, Daniel A.; Oubridge, Chris; Leung, Adelaine K. W.; Li, Jade; Nagai, Kiyoshi (2009-03-26). "Crystal structure of human spliceosomal U1 snRNP at 5.5 A resolution". Nature. 458 (7237): 475–480. Bibcode:2009Natur.458..475P. doi:10.1038/nature07851. ISSN 1476-4687. PMC 2673513. PMID 19325628.
  10. ^ Kondo, Yasushi; Oubridge, Chris; van Roon, Anne-Marie M.; Nagai, Kiyoshi (2015-01-02). "Crystal structure of human U1 snRNP, a small nuclear ribonucleoprotein particle, reveals the mechanism of 5' splice site recognition". eLife. 4. doi:10.7554/eLife.04986. ISSN 2050-084X. PMC 4383343. PMID 25555158.
  11. ^ Galej, Wojciech P.; Oubridge, Chris; Newman, Andrew J.; Nagai, Kiyoshi (2013-01-31). "Crystal structure of Prp8 reveals active site cavity of the spliceosome". Nature. 493 (7434): 638–643. Bibcode:2013Natur.493..638G. doi:10.1038/nature11843. ISSN 1476-4687. PMC 3672837. PMID 23354046.
  12. ^ Nguyen, Thi Hoang Duong; Li, Jade; Galej, Wojciech P.; Oshikane, Hiroyuki; Newman, Andrew J.; Nagai, Kiyoshi (2013-06-04). "Structural basis of Brr2-Prp8 interactions and implications for U5 snRNP biogenesis and the spliceosome active site". Structure. 21 (6): 910–919. doi:10.1016/j.str.2013.04.017. ISSN 1878-4186. PMC 3677097. PMID 23727230.
  13. ^ Nguyen, Thi Hoang Duong; Galej, Wojciech P.; Bai, Xiao-chen; Savva, Christos G.; Newman, Andrew J.; Scheres, Sjors H. W.; Nagai, Kiyoshi (2015-07-02). "The architecture of the spliceosomal U4/U6.U5 tri-snRNP". Nature. 523 (7558): 47–52. Bibcode:2015Natur.523...47N. doi:10.1038/nature14548. ISSN 1476-4687. PMC 4536768. PMID 26106855.
  14. ^ Nguyen, Thi Hoang Duong; Galej, Wojciech P.; Bai, Xiao-Chen; Oubridge, Chris; Newman, Andrew J.; Scheres, Sjors H. W.; Nagai, Kiyoshi (2016-02-18). "Cryo-EM structure of the yeast U4/U6.U5 tri-snRNP at 3.7 Å resolution". Nature. 530 (7590): 298–302. Bibcode:2016Natur.530..298N. doi:10.1038/nature16940. ISSN 1476-4687. PMC 4762201. PMID 26829225.
  15. ^ Fica, Sebastian M.; Nagai, Kiyoshi (2017-10-05). "Cryo-electron microscopy snapshots of the spliceosome: structural insights into a dynamic ribonucleoprotein machine". Nature Structural & Molecular Biology. 24 (10): 791–799. doi:10.1038/nsmb.3463. ISSN 1545-9985. PMC 6386135. PMID 28981077.
  16. ^ Scheres, Sjors Hw; Nagai, Kiyoshi (2017). "CryoEM structures of spliceosomal complexes reveal the molecular mechanism of pre-mRNA splicing". Current Opinion in Structural Biology. 46: 130–139. doi:10.1016/j.sbi.2017.08.001. ISSN 1879-033X. PMID 28888105.
  17. ^ "Kiyoshi Nagai | Royal Society". royalsociety.org. Retrieved 2018-12-09.
  18. ^ Newman, Andy; Luisi, Ben (2022). "Kiyoshi Nagai. 25 June 1949—27 September 2019". Biographical Memoirs of Fellows of the Royal Society. 72: 275–291. doi:10.1098/rsbm.2021.0043. S2CID 247453651.
  19. ^ "Find people in the EMBO Communities". people.embo.org. Retrieved 2018-12-09.
  20. ^ Nagai, K.; Muto, Y.; Pomeranz Krummel, D. A.; Kambach, C.; Ignjatovic, T.; Walke, S.; Kuglstatter, A. (2001). "Structure and assembly of the spliceosomal snRNPs. Novartis Medal Lecture". Biochemical Society Transactions. 29 (Pt 2): 15–26. doi:10.1042/bst0290015. ISSN 0300-5127. PMID 11356120.
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