Zhang, X., Vadas, O., Perisic, O., Anderson, K.E., Clark, J., Hawkins, P.T., Stephens, L.R., Williams, R.L. (2011)
Structure of lipid kinase p110β/p85 elucidates a novel SH2-domain mediated inhibitory mechanism.
Mol. Cell 41:567-578.
Berndt, A., Miller, S., Williams, O., Le, D.D., Houseman, B.T., Pacold, J.I., Gorrec, F., Hon, W.C., Ren, P., Liu, Y., Rommel, C., Gaillard, P., Ruckle, T., Schwarz, M.K., Shokat, K.M., Shaw, J.P., Williams, R.L. (2010)
The p110 delta structure: mechanisms for selectivity and potency of new PI(3)K inhibitors.
Nat. Chem. Biol. 6(2): 117-124.
Miller S., Tavshanjian B., Oleksy A., Perisic O., Houseman B.T., Shokat K.M., Williams R.L. (2010)
Shaping development of autophagy inhibitors with the structure of the lipid kinase Vps34.
Science 327(5973):1638-1642.
Samson, R.Y., Obita, T., Freund, S.M., Williams, R. L., Bell, S.D. (2008)
A Role for the ESCRT System in Cell Division in Archaea.
Science 322: 1710-1713.
Obita, T., Saksena,S., Ghazi-Tabatabai,S., Gill,D.J., Perisic, O., Emr, S. & Williams,R.L. (2007)
Structural basis for selective recognition of ESCRT-III by the AAA-ATPase Vps4.
Nature 449: 735-739.
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Group Members
- Olga Perisic
- Yohei Ohashi
- Alex Berndt
- Nicolas Soler
- Michael Wilson
- John Burke
- Oscar Vadas
- Lufei Zhang
- Michiel Hadders
- Domagoj Baretic
- Glenn Masson
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Most receptor-mediated signal transduction pathways in mammalian cells involve enzymes that generate either soluble or membrane-resident second messengers by modifying phospholipids present in cell membranes. These enzymes are activated in response to a variety of cellular signals such as hormones, cytokines and neurotransmitters.
We are trying to develop a detailed structural understanding of the network of interacting pathways involved in phospholipid signalling.
We are determining the structures of endosomal and autophagosomal protein complexes.
In addition to X-ray crystallography, we are using electron microscopy, protein engineering, biophysical methods and in vivoassays to characterise these regulatory interactions.
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Our current efforts focus on phosphoinositide 3-kinases and their downstream effectors. Due to their frequent mutation in human cancers and their roles in the immune systems, a structural understanding of class I PI3Ks is important for drug development.
Amongst many cellular processes regulated by specific phospholipid recognition are membrane protein sorting into multivesicular bodies (MVB) and autophagy, which are dependent on 3-phosphoinositides derived from class III PI3Ks.
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Group Leaders 
