Waksman, Gabriel
Professor of Structural Molecular Biology
所属大学: Birkbeck, University of London
所属学院: Department of Biological Sciences
邮箱:
g.waksman@mail.cryst.bbk.ac.uk
个人主页:
http://www.bbk.ac.uk/biology/our-staff/academic/gabriel-waksman
研究领域
Pilus biogenesis
Bacterial pili are hair-like surface-exposed organelles. They are responsible for recognition of and attachment to the host and thus, are also crucial virulence factors. Pili are polymer of protein subunits, the assembly of which require accessory proteins. There are two biogenesis pathways for the production of pili in Gram-negative bacteria: the chaperone-usher pathway and the type IV pilus biogenesis pathway - not to be confused with T4S systems! We are engaged in research on both, but have made most progress on the former. Chaperone-usher (CU) pili have clear relevance in the pathogenicity of uropathogenic Escherichia coli, where CU pili mediate bacterial tropism to the bladder to cause cystitis or to the kidney to cause pyolenephritis. CU pili require two accessory proteins for biogenesis: a chaperone that stabilises pilus subunits and ferries them to an assembly platform, the usher, the second accessory protein required in this system. The usher is an extraordinary molecular nanomachine embedded in the outer membrane. It drives subunit recruitment, polymerisation and secretion. All in one protein
近期论文
TR. Costa, A. Ilangovan, M. Ukleja, A. Redzej, JM. Santini, TK. Smith, EH. Egelman, G. Waksman (2016). Structure of the Bacterial Sex F Pilus Reveals an Assembly of a Stoichiometric Protein-Phospholipid Complex. Cell. 166(6):1436-1444.e10 M. Hospenthal, A. Redzej, K. Dodson, M. Ukleja, B. Frenz, C. Rodrigues, S. Hultgren, F. DiMaio, E. Egelman and G. Waksman (2016). Structure of a Chaperone-Usher Pilus Reveals the Molecular Basis of Rod Uncoiling. Cell. 164:269-278. HH.Low , F. Gubellini, A. Rivera-Calzada, N. Braun, S. Connery, A. Dujeancourt, F. Lu, A. Redzej, R. Fronzes, EV. Orlova, G. Waksman (2014) Structure of a type IV secretion system. Nature. 2014 Apr 24;508(7497):550- 3. doi: 10.1038/nature13081. Epub 2014 Mar 9. PMID: 24670658 S. Geibel, E. Procko, S.J. Hultgren, D. Baker, and G. Waksman (2013) Structure and energetic basis of folded protein transport by the FimD usher. Nature. 496:243-246. G. Phan, H. Remaut, T.Wang, W. Allen, K. Pirker, A. Lebedev, N. Henderson, S. Geibel, E. Volkan, J. Yan, M. Kunze, J. Pinkner, B. Ford, C. Kay, H. Li, S. Hultgren, D. Thanassi, and G. Waksman (2011) Crystal structure of the FimD usher bound to its cognate FimC:FimH substrate. Nature. 474:49-53. Chandran, R. Fronzes, S. Duquerroy, N. Cronin, J. Navaza, and G. Waksman (2009) Crystal structure of the outer membrane complex of a type IV secretion system. Nature. 462:1011-1015. R. Fronzes, E. Schaefer, H. Saibil, E. Orlova and G. Waksman (2009) Structure of type IV secretion core complex. Science. 323:266-268. H. Remaut, C. Tang, N.S. Henderson, J.S. Pinkner, T. Wang, S.J. Hultgren, D.G. Thanassi, G. Waksman, H. Li (2008) Fiber Formation Across the Bacterial Outer Membrane by the Chaperone/Usher Pathway. Cell. 133:640-652. First author (H. Remaut) member of the Waksman lab F. G. Sauer, J. Pinkner, G. Waksman, and S.J.Hultgren (2002) Chaperone Priming of Pilus Subunit Facilitates a Topological Transition that Drives Fiber Formation. Cell. 111:543-51. Waksman sole corresponding author K.W. Dodson, J.S. Pinkner, T. Rose, G. Magnusson, S.J. Hultgren, and G. Waksman (2001) Structural Basis of Tropism of Pyelonephritic /E. coli/ for the Human Kidney. Cell. 105:733–743. F.G. Sauer, K. Fütterer, J.S. Pinkner, K.W. Dodson, S.J. Hultgren, and G. Waksman (1999) Structural basis of chaperone function and pilus biogenesis. Science. 285:1058-1061. S. Korolev, J. Hsieh, G. Gauss, T.M. Lohman, and G. Waksman (1997) Major domain swivelling revealed by the crystal structure of binary and ternary complexes of /E.coli/ Rep helicase bound to single-stranded DNA and ADP. Cell. 90:635-647. D. Ornitz, A. Herr, M. Nillson, J. Westman, C-M. Svahn, and G. Waksman (1995) FGF binding and FGF receptor activation by synthetic heparan-derived di- and trisaccharides. Science. 268:432-436. G. Waksman, S. Shoelson, N. Pant, D. Cowburn, and J. Kuriyan. (1993) Binding of a high affinity phosphotyrosyl peptide to the src SH2 domain: crystal structures of the complexed and peptide-free forms. Cell. 72:779-790. G. Waksman, D. Kominos, S. Robertson, N. Pant, D. Baltimore, R.Birge, D. Cowburn, H. Hanafusa, B. Mayer, M. Overduin, M. Resh, C. Rios, L. Silverman and J. Kuriyan (1992) Crystal structure of the phosphotyrosine recognition domain SH2 of v-src complexed with tyrosine-phosphorylated peptides. Nature. 358:646-653.