Structural Biology and Small-molecule Design
Revealing the molecular and atomic details of protein function and regulation is imperative when trying to develop drugs that will accurately intervene with cellular processes. Our lab focuses on the mechanistic details of regulation in proteins that are central to physiological and pathophysiological processes. We aim to unveil the relationship between ligand-binding, dynamics, activation and transduction of signals, and to manipulate these processes using allosteric small-molecule modulators. This calls for a multidisciplinary approach that involves structural characterization via x-ray crystallography and electron microscopy, bioinformatics and small-molecule design. This combination of tools will be exerted on flexible proteins with multilayered regulation that have been recalcitrant to mechanistic analysis, such as platelet surface receptors that are key players in homeostasis, immunology and cancer.
1. R. Mor-Cohen, N. Rosenberg, Y. Einav, E. Zelzion, M. Landau, W. Mansour, Y. Averbukh and U. Seligsohn. Unique disulfide bonds in the epidermal growth factor (EGF) domains of β3 affect the structure and function of αIIbβ3 and αvβ3 integrins in a different manner. J Biol Chem 16;287(12):8879-91; 2012.
2. A. Laganowsky, C. Lui, M.R. Sawaya, J.P. Whitelegge, J. Park, M. Zhao, A. Pensalfini, A.B. Soriaga, M. Landau, P.K. Teng, D. Cascio, C. Glabe, D. Eisenberg. Atomic View of a Toxic Amyloid Small Oligomer. Science 335(6073):1228-31; 2012.
• This publication was covered by Science in a “perspective” article: Visualizing Amyloid Assembly, Science 336 (6079) pp. 308-309; 2012.
• This publication was covered in “This week in Science”: A Toxic Barrel, Science 335 (6073) p. 1146; 2012.
• This publication was covered at the Alzheimer Research Forum
3. JP. Colletier*, A. Laganowsky*, M. Landau*, M. Zhao*, A.B. Soriaga*, L. Goldschmidt, D. Cascio, M.R. Sawaya, and D. Eisenberg. Molecular Basis for Amyloid-beta Polymorphism. PNAS 108(41):16938-43; 2011. *Authors contributed equally
• This publication was covered at the Alzheimer Research Forum:
4. M. Landau, M.R. Sawaya, K.F. Faull, A. Laganowsky, L. Jiang, S.A. Sievers, J. Liu, J.R. Barrio and D. Eisenberg. Towards a Pharmacophore for Amyloid. PLoS Biology 9(6): e1001080; 2011.
• This publication was selected by Nature Chemical Biology as their “choices from the recent literature”.
• This publication was covered in the UCLA newsroom
5. M. Landau and N. Rosenberg. Molecular Insight into Human Platelet Antigens: Structural and Evolutionary Conservation Analyses offer New Perspective to Immunogenic Disorders. Transfusion 51(3):558-69; 2010.