Lectures & Reports
Structure Biology of Sirtuins2016/11/26

Title: Structure Biology of Sirtuins

Speaker: Prof.Rui-Ming Xu

Time: 2:00PM, Dec. 1, 2016

Venue:114,College of Pharmacy


About the speaker: Rui-Ming Xu

Address: Institute of Biophysics Chinese Academy of Sciences,15 Datun Road, Chaoyang District,Beijing 100101, China

E-mail: rmxu@sun5.ibp.ac.cn

Phone:  86-10-64888797

Fax:  86-10-64888513

Education

Zhejiang University, Hangzhou, China B.Sc. 1984 Physics

Brandeis University, Waltham, MA M.A. 1985 Physics

Brandeis University, Waltham, MA Ph.D. 1990 Physics

Positions Held

1984 - 1989 Graduate Research, Brandeis University (with L.F. Abbott & M.T. Grisaru)

1989 - 1991 Postdoctoral Fellow, University of Texas at Austin (with Steven Weinberg)

1991 - 1993 Postdoctoral Associate, SUNY at Stony Brook (with Chen Ning Yang)

1993 - 1994 Visiting Scientist, Cold Spring Harbor Laboratory (with Xiaodong Cheng)

1994 - 1996 Staff Associate II, Cold Spring Harbor Laboratory (with Xiaodong Cheng)

1996 - 2000 Assistant Professor, Cold Spring Harbor Laboratory

1998 - 2006 Faculty member, Genetics and Biophysics programs at Stony Brook University

2000 - 2004 Associate Professor, Cold Spring Harbor Laboratory

2005 - 2006 Professor, Cold Spring Harbor Laboratory

2006 - 2008 Professor, Skirball Institute of Biomolecular Medicine & Department of

Pharmacology, NYU School of Medicine (Adjunct Professor since 1/1/2009)

2009 - Investigator, Institute of Biophysics, Chinese Academy of Sciences (CAS);

and Director designate, National Laboratory of Protein Science, Beijing, China

2010 - 2012 Deputy Director, Institute of Biophysics (IBP), CAS

2011 - Director, National Laboratory of Biomacromolecules, IBP, CAS

2012 - 2013 Director, Bureau of Life Sciences and Biotechnology, CAS

2013 - 2015 Director, Bureau of Frontier Sciences and Education, CAS

2015 - Deputy Director, Institute of Biophysics (IBP), CAS

Awards and Honors

1984 China-U.S. Physics Examination and Application (CUSPEA) Fellow

1984 Outstanding Thesis Award, Zhejiang University

2008 National “Thousand-person Plan” Award

2009 Great Wall Professorship, Chinese Academy of Sciences-Novo Nordisk

2009 Outstanding Young Investigator Award, Natural Science Foundation of China

2012 Fellow, the American Association for the Advancement of Science (AAAS)

Professional Services

1998 - 2004 Spokesperson, beamline X26C, National Synchrotron Light Source, BNL

1998 Mail-in grant reviewer for the NIH Biochemistry study section

1999, 2003 Mail-in grant reviewer for The Wellcome Trust, UK

2001 Mail-in reviewer for American Chemical Society Petroleum Research Fund

2001, 2003, 2004 Ad hoc reviewer, NIH study section BBCB

2001 - 2004 Biology Proposal Study Panel, NSLS, BNL (chair, 2003-2004)

2003 Review panel, NIH study section ZRG1 SSS-B

2007 Review panel, NIH study section ZAG1 ZIJ-5

2007 Member of assessment panel, China Fellows Program of Cancer Research UK

2008 Review panel, NIH study section ZGM1 BRT-9 (KR)

2007 - Member of Editorial Board, Genes & Development

2008 - Member of Editorial Board, Science in China, Series C: Life Sciences

2008 - 2014 Vice President, Cold Spring Harbor Asia

2009 - Member of Executive Committee, Chinese Crystallographic Society

2009 - Member of Executive Committee, and Director of Molecular Biophysics

Section, the Chinese Biophysical Society

2010 - Deputy editor-in-chief, Protein & Cell

2010, 2012, 2014 Co-organizer, Cold Spring Harbor Asia Meeting on “Epigenetics, Chromatin

& Transcription”

2011 - 2014 Vice president, The Chinese Protein Society

2011 - Member of Editorial Board, BBA-Gene Regulatory Mechanisms

2013 - Vice president, the Chinese Biophysical Society

2014 Ad hoc reviewer, NSF-Molecular and Cellular Biosciences

2014 - Faculty of F1000prime in Nuclear Structure & Function

2014 - Vice president, the Chinese Society of Biochemistry and Molecular Biology

2015 - Member of Editorial Board, Structure

2016 - Member of Editorial Board, Epigenetics & Chromatin

Peer Reviewed Publications

1. R.M. Xu, G. Carmel, R.M. Sweet, J. Kuret, and X. Cheng (1995) Crystal structure of casein

kinase-1, a phosphate-directed protein kinase. EMBO J. 14, 1015-1023.

2. R.M. Xu, G. Carmel, J. Kuret, and X. Cheng (1996) Structural basis for selectivity of the

isoquinoline sulfonamide family of protein kinase inhibitors. Proc. Natl. Acad. Sci. USA, 93,

6308-6313.

3. R.M. Xu, C. Koch, Y. Liu, J.R. Horton, D. Knapp, K. Nasmyth, and X. Cheng (1997) Crystal

structure of the DNA-binding domain of Mbp1, a transcription factor important in cell cycle

control of DNA synthesis. Structure 5, 349-358.

4.  L. Jokhan, A.P. Dong, A. Mayeda, A.R. Krainer, and R.M. Xu (1997) Crystallization and

preliminary X-ray diffraction studies of UP1, the two-RRM domain of hnRNP A1. Acta Cryst.

D53, 615-618.

5. R.M. Xu, L. Jokhan, X. Cheng, A. Mayeda, and A.R. Krainer (1997) Crystal structure of human

UP1, the domain of hnRNP A1 that contains two RNA-recognition motifs. Structure 5, 559-570.

6.  A. Mayeda, S.H. Munroe, R.M. Xu, and A.R. Krainer (1998) Distinct functions of the closely

related tandem RNA recognition motifs of hnRNP A1. RNA 4, 1111-1123.

7. J. Jiang, Y. Zhang, A.R. Krainer, and R.M. Xu (1999) Crystal structure of human p32, a

doughnut-shaped acidic mitochondrial matrix protein. Proc. Natl. Acad. Sci. USA 96, 3572-3577.

8. J. Ding, M.K. Hayashi, A.R. Krainer, and R.M. Xu (1999) Crystal structure of the two-RRM

domain hnRNP A1 (UP1) complexed with single-stranded telomeric DNA. Genes & Dev. 13,

1102-1115.

9. J.P.J. Chong, M.K. Hayashi, M.N. Simon, R.M. Xu, and B. Stillman (2000) A double hexamer

archaeal minichromosome maintenance protein is an ATP dependent DNA helicase. Proc. Natl.

Acad. Sci. USA 97, 1530-1535.

10. J. Jiang, D.S. Horowitz, and R.M. Xu (2000) Crystal structure of the functional domain of the

splicing factor Prp18. Proc. Natl. Acad. Sci. USA 97, 3022-3027.

11. J. Min, J. Landry, R. Sternglanz, and R.M. Xu (2001) Crystal structure of a SIR2 homolog-NAD

complex. Cell 105, 269-279.

12. J. Vitali, J. Ding, J. Jiang, Y. Zhang, A.R. Krainer, and R.M. Xu (2002) Correlated Alternative

Side-chain Conformations in the RNA-Recognition Motif of hnRNP A1. Nucleic Acids Res. 30,

1531-1538.

13.  Z. Zhang, M.K. Hayashi, O. Merkel, B. Stillman, and R.M. Xu (2002) Structure and function of

the BAH domain of ORC1 in transcriptional silencing. EMBO J. 21, 4600-4611.

14. H.H Ng, R.M. Xu, Y. Zhang, and K. Struhl (2002) Ubiquitination of histone H2B by Rad6 is

required for efficient Dot1-mediated methylation of histone H3-Lysine 79. J. Biol. Chem. 277,

34655-34657.

15. J. Min, X. Zhang, X. Cheng, S.I. Grewal, and R.M. Xu (2002) Structure of the SET domain

histone lysine methyltransferase Clr4. Nat. Struct. Biol. 9, 828-832.

16. J. Min, Q. Feng, Z. Li, Y, Zhang, and R.M. Xu (2003) Structure of the catalytic domain of

human Dot1L, a non-SET domain nucleosomal histone methyltransferase. Cell 112, 711-723.

17. H. Shi and R.M. Xu (2003) Crystal structure of the Drosophila Mago nashi -Y14 complex.

Genes & Dev. 17, 971-976.

18. J. Min, Y. Zhang, and R.M. Xu (2003) Structural basis for specific binding of Polycomb

chromodomain to histone H3 methylated at lysine 27. Genes & Dev. 17, 1823-1828.

19. J. Landry, A. Sutton, T. Hesman, J. Min, R.M. Xu, M. Johnston, and R. Sternglanz (2003) Set2-

catalyzed methylation of histone H3 represses basal expression of GAL4 in S. cerevisiae. Mol.

Cell Biol. 23, 5972-5978.

20. H. Chiodi, M. Corioni, M. Giordano, R. Valgardsdottir, F. Cobianchi, R.M. Xu, S. Riva, and G.

Biamonti (2004) RNA binding domain 2 directs the recruitment of SF2/ASF to nuclear stress

bodies. Nucleic Acids Res. 32, 4127-4136.

21. H. Shi, O. Cordin, C.M. Minder, P. Linder, and R.M. Xu (2004) Crystal structure of the human

ATP-dependent splicing and export factor UAP56. Proc. Natl. Acad. Sci. USA 101, 17628-

17633.

22. H.C. Hsu, B. Stillman, and R.M. Xu (2005) Structural basis for origin recognition complex 1

protein-silencing regulator 1 protein interaction in epigenetic silencing. Proc. Natl. Acad. Sci.

USA 102, 8519-8524.

23. G. Hu, G. Lin, M. Wang, J. Jiang, R.M. Xu, C. Nathan, and H. Li (2006) Structure of the

Mycobacterium tuberculosis proteasome and mechanism of inhibition by a peptidyl boronate.

Mol. Microbiology 59, 1417-1428.

24. Y. Huang, M.P. Myers, and R.M. Xu (2006) Structure of the EMSY-HP1 complex reveals a

new mode of HP1 binding. Structure 14, 703-712.

25. J.J. Connelly, P. Yuan, H.C. Hsu, Z. Li, R.M. Xu*, and R. Sternglanz* (2006) Structure and

function of the yeast Sir3 BAH domain. Mol. Cell Biol. 26, 3256-3265. *Co-corresponding

authors.

26. Q.-S. Zhang, L. Manche, R.M. Xu, and A. R. Krainer (2006) HnRNP A1 associates with

telomere ends and stimulates telomerase activity by facilitating the translocation step. RNA 12,

1116-1128.

27. Y. Huang, J. Fang, M.T. Bedford, Y, Zhang, and R.M. Xu (2006) Recognition of histone H3

Lysine-4 methylation by the double tudor domain of JMJD2A. Science 312, 748-751.

28.  Z. Li, R. Cao, M. Wang, M.P. Myers, Y. Zhang, and R.M. Xu (2006) Structure of a Bmi-1-

Ring1B Polycomb group ubiquitin ligase complex. J. Biol. Chem. 281, 20643-20649.

29.  J. Han, H. Zhou, B. Horazdovsky, K. Zhang, R.M. Xu, and Z. Zhang (2007) Rtt109 acetylates

histone H3 lysine 56 and functions in DNA replication. Science 315, 653-655.

30. J. Han, H. Zhou, Z. Li, R.M. Xu, and Z. Zhang (2007) The Rtt109-Vps75 histone

acetyltransferase complex acetylates non-nucleosomal histone H3. J. Biol. Chem. 282, 14158-

14164.

31. X. Yang, J. Zhou, L. Sun, Z. Wei, J. Gao, W. Gong, R.M. Xu, Z. Rao, and Y. Liu (2007)

Rui-Ming Xu

Structural basis for DCN-1’s function in protein neddylation. J. Biol. Chem. 282, 24490-24494.

32. J. Han, H. Zhou, Z. Li, R.M. Xu, and Z. Zhang (2007) Acetylation of lysine 56 of histone H3

catalyzed by Rtt109 and regulated by Asf1 is required for replisome integrity. J. Biol. Chem. 282,

28587-28596.

33. H.P. Harding, J.G. Lackey, H.C. Hsu, Y. Zhang, J. Deng, R.M. Xu, M.J. Dhama, and D. Ron

(2008) An intact unfolded protein response in Trpt1 knockout mice reveals phylogenetic

divergence in pathways for RNA ligation. RNA 14, 225-232.

34.  M.K. Hayashi, C. Tang, C. Verpelli, R. Narayanan, M.H. Sterns, R.M. Xu, H. Li, C. Sala, and Y.

Hayashi (2009) Structural framework of the postsynaptic density formed by a high-order

complex between Homer and Shank. Cell 137, 159-171.

35. Y. Li, P. Trojer, C.F. Xu, P. Cheung, A. Kuo, W.J. 3rd, Drury, Q. Qiao, T.A. Neubert, R.M. Xu,

O. Gozani, and D. Reinberg (2009) The target of the NSD family of histone lysine methyl

transferases depends on the nature of the substrate. J. Biol. Chem. 284, 34283-95.

36. H. Liu, J.Y. Wang, Y. Huang, Z. Li, W. Gong, R. Lehmann, and R.M. Xu (2010) Structural

basis for methylarginine-dependent recognition of Aubergine by Tudor. Genes & Dev 24, 1876-

81.

37. Q. Qiao, Y. Li, Z. Chen, M. Wang, D. Reinberg, and R.M. Xu (2011) The structure of NSD1

reveals an autoregulatory mechanism underlying histone H3K36 methylation. J. Biol. Chem. 286,

8361-8.

38.  D. Su, Q. Hu, H. Zhou, J.R. Thompson, R.M. Xu, Z. Zhang, and G. Mer (2011) Structure and

histone binding properties of the Vps75-Rtt109 chaperone-lysine acetyltransferase complex. J.

Biol. Chem. 286, 15625-9.

39. H. Hu, Y. Liu, M. Wang, J. Fang, H. Huang, N. Yang, Y. Li, J. Wang, X. Yao, Y. Shi, G. Li, and

R.M. Xu (2011) Structure of a CENP-A-Histone H4 heterodimer in complex with chaperone

HJURP. Genes & Dev. 25, 901-6.

40. W. Wang, Z. Chen, Z. Mao, H. Zhang, X. Ding, S. Chen, X. Zhang, R.M. Xu, B. Zhu (2011)

Nucleolar protein Spindlin1 recognizes H3K4 methylation and stimulates the expression of

rRNA genes. EMBO Rep. 12, 1160-1166.

41. L. Sun, M. Wang, Z. Lv, N. Yang, Y. Liu, S. Bao, W. Gong, and R.M. Xu (2011) Structural

insights into protein arginine symmetric dimethylation by PRMT5. Proc. Natl. Acad. Sci. USA

108, 20538-20543.

42. K. Liu, C. Bian, H. Liu, Y. Guo, R. Lam, F. MacKenzie, L.A. Rojas, D. Reinberg, M. Bedford,

R.M. Xu*, and J. Min* (2012) Crystal structure of TDRD3 and methyl-arginine binding

characterizations of TDRD3, SMN and SPF30. PLoS ONE 7, e30375. *Co-corresponding

authors.

43.  P.C. Lin, and R.M. Xu (2012) Structure and assembly of the SF3a splicing factor complex of U2

snRNP. EMBO J. 31, 1579-1590.

44.  L. Wang, F. Wang, D. Zhang, Z. Chen, R.M. Xu, K.H. Nierhaus, W. Gong, and Y. Qin (2012) A

conserved proline switch on the ribosome facilitates the recruitment and binding of trGTPases.

Nat. Struct. Mol. Biol. 19, 403-410.

45. N. Yang, W. Wang, Y. Wang, M. Wang, Q. Zhao, Z. Rao, B. Zhu, and R.M. Xu (2012) Distinct

mode of methylated lysine-4 of histone H3 recognition by tandem tudor-like domains of

Spindlin1. Proc. Natl. Acad. Sci. USA 109, 17954-17959.

46. C.P. Liu, C. Xiong, M. Wang, Z. Yu, N. Yang, P. Chen, Z. Zhang, G. Li, and R.M. Xu (2012)

Structure of the variant histone H3.3-H4 heterodimer in complex with its chaperone DAXX, Nat.

Struct. Mol. Biol. 19, 1287-1292.

47. H.C. Hsu, C.L. Wang, M. Wang, N. Yang, Z. Chen, R. Sternglanz, and R.M. Xu (2013)

Structural basis for allosteric stimulation of Sir2 activity by Sir4 binding. Genes & Dev. 27, 64-

73.

48. N. Yang and R.M. Xu (2013) Structure and function of the BAH domain in chromatin biology.

Crit. Rev. Biochem. Mol. Biol. 48, 211-221.

49.  D. Yang, Q. Fang, M. Wang, R. Ren, H. Wang, M. He, Y. Sun, N. Yang, and R.M. Xu (2013)

N?-acetylated Sir3 stabilizes the conformation of a nucleosome-binding loop in the BAH

domain. Nat. Struct. Mol. Biol. 20, 116-118.

50. M. Wang, R.M. Xu, and P.R. Thompson (2013) Substrate specificity, processivity, and kinetic

mechanism of protein arginine methyltransferase 5. Biochemistry 52, 5430-40.

51. F. Song, P. Chen, D. Sun, M. Wang, L. Dong, D. Liang, R.M. Xu, P. Zhu, and G. Li (2014)

Cryo-EM study reveals a double helix of the 30 nm chromatin fiber twisted by tetra-nucleosomal

units. Science 344, 376-380.

52. T. Zhou, J. Xiong, M. Wang, N. Yang, J. Wong, B. Zhu, and R.M. Xu (2014) Structural basis

for hydroxymethylcytosine recognition by the SRA domain of UHRF2. Mol. Cell 54, 879-886.

53.  R. Ren, H Liu, W. Wang, M. Wang, N. Yang, Y.H. Dong, W. Gong, R. Lehmann, and R.M. Xu

(2014) Structure and domain organization of Drosophila Tudor. Cell Res. 24, 1146-1149.

54. Y. Li, L. Zhang, T. Liu, C. Chai, Q. Fang, H. Wu, P.A. Agudelo Garcia, Z. Han, S. Zong, Y. Yu,

X. Zhang, M.R. Parthun, J. Chai, R.M. Xu, and M. Yang (2014) Hat2p recognizes histone H3

tail to specify the acetylation of the newly synthesized H3/H4 heterodimer by the Hat1p/Hat2p

complex. Genes & Dev. 28, 1217-1227.

55. Z . Yu, X. Zhou, W. Wang, W. Deng, J. Fang, H. Hu, Z. Wang, S. Li, L. Cui, J. Shen, L. Zhai, S.

Peng, J. Wong, S. Dong, Z. Yuan, G. Ou, X. Zhang, P. Xu, J. Lou, N. Yang, P. Chen, R.M. Xu,

and G. Li (2015) Dynamic phosphorylation of CENP-A at Ser68 orchestrates its cell cycledependent

deposition at centromeres. Dev. Cell 32, 68-81.

56. J. Fang, Y. Wei, Y. Liu, W. Deng, Z. Yu, L. Huang, Y. Teng, T. Yao, Q. You, H. Ruan, P. Chen,

R.M. Xu, and G. Li (2015) Structural transitions of centromeric chromatin regulate the cell

cycle-dependent recruitment of CENP-N. Genes & Dev. 29, 1058-1073.

57. D. Cao, M. Wang, X. Qiu, D. Liu, H. Jiang, N. Yang*, and R.M. Xu* (2015) Structural basis for

allosteric, substrate-dependent stimulation of SIRT1 activity by resveratrol. Genes & Dev. 29,

1316-1325.

58. H. Wang, M. Wang, N. Yang*, and R.M. Xu* (2015) Structure of the quaternary complex of

histone H3-H4 heterodimer with chaperone ASF1 and the replicative helicase subunit MCM2.

Protein & Cell 6, 693-697.

59. N. Yang*, Z. Yu, M. Hu, M. Wang, R. Lehmann*, and R.M. Xu* (2015) Structure of

Drosophila Oskar reveals a novel RNA binding protein. Proc. Natl. Acad. Sci. USA 112, 11541-

11546.

60. G. Gao, M. Wang, N. Yang, Y. Huang, and R.M. Xu (2015) Structure of Zeste-DNA complex

reveals a new modality of DNA recognition by homeodomain-like proteins. J. Mol. Biol. 427,

3824-3833.

61. Q. Fang, P. Chen, M. Wang, J. Fang, N. Yang, G. Li*, and R.M. Xu* (2016) Human

cytomegalovirus IE1 protein alters the higher-order chromatin structure by targeting the acidic

patch of the nucleosome. eLife 5, e11911.

62.  W. Fu, N. Liu, Q. Qiao, M. Wang, J. Min, B. Zhu*, R.M. Xu*, and N. Yang* (2016) Structural

basis for substrate preference of SMYD3, a SET domain-containing protein lysine

methyltransferance. J. Biol. Chem. 291, 9173-9180.

63. D. Fang, H. Gan, J.H. Lee, J. Han, Z. Wang, S.M. Riester, L. Jin, J. Chen, H. Zhou, J. Wang, N.

Yang, E.W. Bradley, T. Ho, B.P. Rubin, J.A. Bridge, S.N. Thibodeau, O. Tamas, Y. Chen, A.

van Wijnen, A. Oliveira, R.M. Xu, J.J. Westendorf, and Z. Zhang (2016) The histone

H3.3K36M mutation reprograms the epigenome of chondroblastomas. Science 352, 1344-1348.

64.W. Jin, Y. Wang, C.P. Liu, N. Yang, M. Jin, Y. Cong, Mingzhu Wang*, and R.M. Xu* (2016)

Structural basis for snRNA recognition by the double WD40-repeat domain of Gemin5. Genes &

Dev. Published online Nov.10 2016.

65. H. Nishino and R.M. Xu (1987) Spacetime supersymmetry breaking in heterotic string theory.

Physics Letters B196, 467-472.

66. M.T. Grisaru and R.M. Xu (1988) Quantum supergravities in two dimensions. Physics Letters

B205, 486-492.

67.  L.F. Abbott, J. Traschen, and R.M. Xu (1988). Integral constraints in general relativity. Nuclear

Physics B296, 710-716.

68. R.M. Xu (1989) BRST quantization of the type II Green-Schwarz string. Intl. J. Mod. Phys. A4,

5185-5203.

69.  R.M. Xu (1990) A sphaleron solution in the CPN-1 model. Physics Letters B238, 333-336.

70.  R.M. Xu (1990) Two-dimensional quantum (0, 2) supergravity. Physics Letters B247, 295-301.

71. R. Leigh, S. Paban, and R.M. Xu (1991) Electric dipole moment of electron. Nuclear Physics

B352, 45-58.

72. R.M. Xu (1991) "Light" Higgs particles and strongly interacting W's and Z's. Physics Letters

B258, 409-414.

73. R.M. Xu (1991) Why is mu/md so much smaller than mc/ms and mt/mb? Physical Review D44,

590-592.

74. A. Soni and R.M. Xu (1992) Electric dipole moment of the top quark in Higgs-Boson-Exchange

models of CP nonconservation. Physical Review Letters 69, 33-36.

75. C. Kao and R.M. Xu (1992) Charged-Higgs-Loop contribution to the electric dipole moment of

electron. Physics Letters B296, 435-439.

76. S. Thomas and R.M. Xu (1992) Light neutrinos from the quark condensate. Physics Letters

B284, 341-346.

77. A. Soni and R.M. Xu (1993) Probing CP violating via Higgs decays to four leptons. Physical

Review D48, 5259-5263.


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