Imperial College London

ProfessorXiaodongZhang

Faculty of MedicineDepartment of Medicine

Professor of Macromolecular Structure and Function
 
 
 
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Contact

 

+44 (0)20 7594 3151xiaodong.zhang Website

 
 
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Location

 

104Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Summary

Mini CV 

  • 1988 - B.Sc. in Physics, Peking University, China
  • 1995 - Ph.D. in Physics, SUNY @ Stony Brook, USA
  • 1995 - 1997 postdoctoral fellow, Harvard University
  • 1997 - 2000 postdoctoral Fellow, Cancer Research UK
  • 2001 - 2005 Lecturer, Imperial College London
  • 2005 - 2008 Reader, Imperial College London
  • 2007 - present, visiting professor, College of Life Sciences, Peking University, China
  • 2008 - 2014, Professor of Macromolecular Structure and Function, Imperial College London
  • 2014 - present, Professor, Section of Structural Biology, Department of Medicine, Imperial College London
  • 2011 - 2014, Director, Centre for Structural Biology, Imperial College london

Research

My research programme focuses on unravelling the mechanisms of macromolecular machines using a range of structural biology techniques including X-ray crystallography and cryo-electron microscopy. I am particularly interested in large macromolecular assemblies invovled in DNA processing as well as the AAA (ATPase Associated with diverse cellular Activities) protein family. At present my research focuses on three main areas: key components in DNA damage response, transcriptional regulation in bacteria, structrue and mechanism of multifunctional p97. 

Structures and Mechanisms of key components in the DNA damage response- DNA is exposed to toxic chemicals, UV and other radiation and consequently tens of thousands of DNA bases are damaged each day in every human cell. Cells have developed sophisticated systems using multi-subunit macromolecular complexes to detect, process and repair this damage in a highly controlled and coordinated fashion. We are currently using a multi-disciplinary approach to provide a molecular understanding of some of the key events including signaling, chromatin remodeling and DNA damage repair itself. This project is in collaboration with Prof. Peter Burgers, Washington University in St Louis, Prof. Dale Wigley FRS and Dr. Stephen West FRS, Cancer Research UK.

Transcription regulation - One of my main research areas is to understand the transcription regulation, in particular the activation/initiation process. We use the bacterial sigma54 dependent system as a simplified model system to establish the structural basis for the transcription initiation, in particular how double stranded DNA is melted out and template strand delivered into the activate site of RNA polymerase. This project is in collaboration with Prof. Martin Buck FRS, Imperial College,  Prof Ray Dixon FRS, John Innes Centre and Prof. Yiping Wang, Peking University, China.

Structure and mechanism of AAA ATPases p97 - p97 is an abundant protein which has been reported to be involved in a myriad of cellular activities including formation of golgi, ER and the nuclear envelope as well as ER associated protein degradation (ERAD). Mutations in p97 have been linked to various diseases and p97 is shown to interact with over 40 protein partners. We are studying the mechanism of p97 and its interactions with a diverse range of cofactors. This is a joint project with Prof. Paul Freemont, Imperial College London.

 

Selected recent publications

 

Yang Y, Darbari VC, Zhang N, Lu D, Glyde R, Wang YP, Winkelman JT, Gourse RL, Murakami KS, Buck M, Zhang X (2015). "Structures of the RNA polymerase-s54 reveal new and conserved regulatory strategies". Science, 349:882-885

Shahid T, Soroka J, Kong EH, Malivert L, McIlwraith MJ, Pape T, West SC, Zhang X (2014) " Structure and mechanism of action of the BRCA2 breast cancer tumor suppressor". Nat. Struct Mol Biol doi: 10.1038/nsmb.2899

Darbari VC, Lawton E, Lu D, Burrows PC, Wiesler S, Joly N, Zhang N, Zhang X*, Buck M* (2014) "Molecular basis of nucleotide-dependent substrate engagement and remodeling by an AAA+ activator". Nucleic Acids Res 42:9249-9261 

 Yeung HO, Förster A, Bebeacua C, Niwa H, Ewens C, McKeown C, Zhang X, Freemont PS (2014). "Inter-ring rotations of AAA ATPase p97 revealed by electron cryomicroscopy". Open Biol 4:130142 

Saravanan M, Wuerges J, Bose D, McCormack EA, Cook NJ, Zhang X and Wigley DB (2012) “Interactions between the nucleosome histone core and Arp8 in the INO80 Chromatin Remodelling Complex”. Proc. Natl. Acad Sci. USA. 2012. 109(51):20883-8 

Bebeacua C, Forster A, McKeown C, Meyer HH, Zhang X* and Freemont P* (2012). "Distrinct conformations of the protein complex p97-Ufd1-Npl4 revealed by electron cryomicroscopy". Proc. Natl. Acad Sci. USA. 2012. 109(4):1098-103.

Klein BJ, Bose D, Baker KJ, Yusoff ZM,  Zhang X*, Murakami KS* (2010). “The RNA polymerase and transcription elongation factor Spt4/5 complex structure”  Proc. Nat. Acad. Sci. USA. Online publication, Dec 27, 2010.

 Lu D, Fillet S, Meng C, Alguel Y, Kloppsteck P, Bergeron L, Krell T, Gallegos, MT, Ramos J, Zhang X (2010). "Crystal structures of TtgV in complex with its DNA operator reveals a general model for cooperative DNA binding of tetrameric gene regulators". Genes Dev. 24(22):2556-65.

Bose D, Pape T, Burrows PC, Rappas M, Wigneshweraraj SR, Buck M, Zhang X. (2008). “Organisation of an activator bound RNA polymerase holoenzyme”. Molecular Cell, 32(3):337-346.

Zhang X*, Wigley DB*. (2008). “The ‘glutamate switch’ provides a link between ATPase activity and ligand binding in AAA+ proteins”. Nat Struct Mol Biol. 15(11):1223-7.

Alguel Y, Meng C, Teran W, Krell T, Ramos JL, Gallegos MT, Zhang X. (2007) "Crystal Structures of Multidrug Binding Protein TtgR in Complex with Antibiotics and Plant Antimicrobials" . J Mol Biol. 369(3):829-40.

Pye, V., Beuron F., Keetch, C., Mckeown, C., Robinson CV., Zhang X*., and Freemont P.* (2007) “ The p97-Ufd1-Npl4 Complex: First Sructural Insights”. Proc. Natl. Acad  Sci  USA. 104(2):467-72.

Rappas M., Schumacher J., Beuron F., Niwa H., Bordes P., Wigneshweraraj SR., Keetch CA, Robinson CV., Buck M., and Zhang X. (2005). "Structural Insights into the Activity of Transcriptional Enhancer-Binding Protein". Science, 307:1972-5.

*joint corresponding author

For more information, visit my group web page on Freemont/Zhang Group

Further Information



 

Elected Member of the European Molecular Biology Organisation (2016)

President of UK Peking University Alumni Association (www.pkuaa.org.uk)

Wellcome Trust Senior Investigator (2012)

Fellow of the Society of Biology (2011)

Royal Society Wolfson Merit Research Award (2011)

Chinese National Science Foundation Oversea Outstanding Young Scientist, Category B (2007)

Human Frontier Science Programme Young Investigator Award (2002-2005)

First Recipient of Gertrude Goldhabor Women in Physics Award (1993)

 

 

Selected Publications

Journal Articles

Shahid T, Soroka J, Kong EH, et al., 2014, Structure and mechanism of action of the BRCA2 breast cancer tumor suppressor, Nature Structural & Molecular Biology, Vol:21, ISSN:1545-9993, Pages:962-968

Bose D, Pape T, Burrows PC, et al., 2008, Organization of an Activator-Bound RNA Polymerase Holoenzyme, Molecular Cell, Vol:32, ISSN:1097-2765, Pages:337-346

Zhang X, Wigley DB, 2008, The 'glutamate switch' provides a link between ATPase activity and ligand binding in AAA plus proteins, Nature Structural & Molecular Biology, Vol:15, ISSN:1545-9985, Pages:1223-1227

Briggs LC, Baldwin GS, Miyata N, et al., 2008, Analysis of nucleotide binding to p97 reveals the properties of a tandem AAA hexameric ATPase, Journal of Biological Chemistry, Vol:283, ISSN:0021-9258, Pages:13745-13752

Bose D, Joly N, Pape T, et al., 2008, Dissecting the ATP hydrolysis pathway of bacterial enhancer-binding proteins, Biochemical Society Transactions, Vol:36, ISSN:0300-5127, Pages:83-88

Yeung HO, Kloppsteck P, Niwa H, et al., 2008, Insights into adaptor binding to the AAA protein p97, Biochemical Society Transactions, Vol:36, ISSN:0300-5127, Pages:62-67

Joly N, Rappas M, Buck M, et al., 2008, Trapping of a transcription complex using a new nucleotide analogue: AMP aluminium fluoride, Journal of Molecular Biology, Vol:375, ISSN:0022-2836, Pages:1206-1211

Alguel Y, Meng C, Teran W, et al., 2007, Crystal structures of multidrug binding protein TtgR in complex with antibiotics and plant antimicrobials, Journal of Molecular Biology, Vol:369, ISSN:0022-2836, Pages:829-840

Rappas M, Bose D, Zhang X, 2007, Bacterial enhancer-binding proteins: unlocking sigma(54)-dependent gene transcription, Current Opinion in Structural Biology, Vol:17, ISSN:0959-440X, Pages:110-116

Pye VE, Beuron F, Keetch CA, et al., 2007, Structural insights into the p97-Ufd1-NpI4 complex, Proceedings of the National Academy of Sciences of the United States of America, Vol:104, ISSN:0027-8424, Pages:467-472

Pye VE, Dreveny I, Briggs LC, et al., 2006, Going through the motions: The ATPase cycle of p97, Journal of Structural Biology, Vol:156, ISSN:1047-8477, Pages:12-28

Beuron F, Dreveny I, Yuan X, et al., 2006, Conformational changes in the AAA ATPase p97-p47 adaptor complex, EMBO Journal, Vol:25, ISSN:0261-4189, Pages:1967-1976

Rappas M, Schumacher J, Niwa H, et al., 2006, Structural basis of the nucleotide driven conformational changes in the AAA(+) domain of transcription activator PspF, Journal of Molecular Biology, Vol:357, ISSN:0022-2836, Pages:481-492

Ramos JL, Martinez-Bueno M, Molina-Henares AJ, et al., 2005, The TetR family of transcriptional repressors, Microbiology and Molecular Biology Reviews, Vol:69, ISSN:1092-2172, Pages:326-+

Rappas M, Schumacher J, Beuron F, et al., 2005, Structural insights into the activity of enhancer-binding proteins, Science, Vol:307, ISSN:0036-8075, Pages:1972-1975

Dreveny I, Kondo H, Uchiyama K, et al., 2004, Structural basis of the interaction between the AAA ATPase p97/VCP and its adaptor protein p47, EMBO Journal, Vol:23, ISSN:0261-4189, Pages:1030-1039

Huyton T, Pye VE, Briggs LC, et al., 2003, The crystal structure of murine p97/VCP at 3.6 angstrom, Journal of Structural Biology, Vol:144, ISSN:1047-8477, Pages:337-348

Bordes P, Wigneshweraraj SR, Schumacher J, et al., 2003, The ATP hydrolyzing transcription activator phage shock protein F of Escherichia coli: Identifying a surface that binds sigma(54), Proceedings of the National Academy of Sciences of the United States of America, Vol:100, ISSN:0027-8424, Pages:2278-2283

Zhang XD, Shaw A, Bates PA, et al., 2000, Structure of the AAA ATPase p97, Molecular Cell, Vol:6, ISSN:1097-2765, Pages:1473-1484

Huyton T, Bates PA, Zhang XD, et al., 2000, The BRCA1 C-terminal domain: structure and function, Mutation Research - DNA Repair, Vol:460, ISSN:0921-8777, Pages:319-332

Rosenthal PB, Zhang X, Formanowski F, et al., 1998, Structure of the haemagglutinin-esterase-fusion glycoprotein of influenza C virus., Nature, Vol:396, ISSN:0028-0836, Pages:92-96

Zhang XD, Morera S, Bates PA, et al., 1998, Structure of an XRCC1 BRCT domain: a new protein-protein interaction module, EMBO Journal, Vol:17, ISSN:0261-4189, Pages:6404-6411

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