The London Research Institute research groups are based at Lincoln’s Inn Fields and Clare Hall. Our major research themes are: the biology of tumours and tissues, cellular regulatory mechanisms and genomic integrity and cell cycle.
Helen Walden : Protein Structure Function
Goals
Post-translational modification of proteins by ubiquitin is involved in virtually every cellular process, from cell-cycle control to the wound response in plants. As well as being a signal for proteasomal destruction of target proteins, ubiquitination controls much of the DNA damage response. Much of the work in the Protein Structure and Function lab centres on understanding the molecular mechanisms underlying the choice of modification (monoubiquitin, multiple monoubiquitin, branched ubiquitin, polyubiquitin through K48, K63, K27), and on the recognition of substrates by the ubiquitination machinery. We employ several disease-related models to address these questions, using a combination of X-ray crystallography and biochemical techniques.
Selected Papers
Walden H, Martinez-Torres RJ. Regulation of Parkin E3 ubiquitin ligase activity. Cell Mol Life Sci. 2012;69(18):3053-67
(Abstract)
Chaugule VK, Burchell L, Barber KR, Sidhu A, Leslie SJ, Shaw GS, Walden H. Autoregulation of Parkin through its ubiquitin-like domain. EMBO J. 2011; 30 2853-2867; doi:10.1038/emboj.2011.204
(Abstract)
Hodson C, Cole AR, Lewis LP, Miles JA, Purkiss A, Walden H. Structural Analysis of Human FANCL, the E3 Ligase in the Fanconi Anemia Pathway. J Biol Chem. 2011;286(37):32628-37
(Abstract)
Cole AR, Lewis LP, Walden H. The structure of FANCL, the catalytic subunit of the Fanconi Anemia core complex. Nat Struct Mol Biol. 2010;17(3):294-8
(Abstract)
Ulrich HD, Walden H. Ubiquitin signalling in DNA replication and repair. Nat Rev Mol Cell Biol. 2010;11(7):479-89
(Abstract)
Zhuang M, Calabrese MF, Liu J, Waddell MB, Nourse A, Hammel M, Miller DJ, Walden H, Duda DM, Seyedin SN, Hoggard T, Harper JW, White KP, Schulman BA. Structures of SPOP-Substrate Complexes: Insights into Molecular Architectures of BTB-Cul3 Ubiquitin Ligases. Molecular Cell. 2009;36:39-50
(Abstract)
Turner SJ, Kedzierska K, Komodromou H, La Gruta NL, Dunstone MA, Webb AI, Webby R, Walden H, Xie W, McCluskey J, Purcell AW, Rossjohn J, Doherty PC. Lack of prominent peptide-major histocompatibility complex features limits repertoire diversity in virus-specific CD8+ T cell populations. Nature Immunol. 2005;6:382-389
(Abstract)
Walden H, Podgorski MS, Huang DT, Miller DW, Howard RJ, Minor DL Jr, Holton JM, Schulman BA. The structure of the APPBP1-UBA3-NEDD8-ATP complex reveals the basis for selective ubiquitin-like protein activation by an E1. Mol Cell. 2003;12:1427-1437
(Abstract)
Walden H, Podgorski MS, Schulman BA. Insights into the ubiquitin transfer cascade from the structure of the activating enzyme for NEDD8. Nature. 2003;422(6929):330-4
(Abstract)
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Helen Walden
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