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.

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/

Education

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

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

References
  1. 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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