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JOÃO MORAIS CABRAL
Cellular membranes are lipid barriers that isolate the cellular chemical environment from the external medium. Movement of ions, metabolites and macromolecules through these lipid barriers is essential for the survival of all cellular organisms. In fact, specific proteins that are inserted in the lipid membrane have evolved to mediate the transport processes. These processes can be classified in two groups, diffusive and active, depending on whether net transport is driven by the electrochemical gradient of the transported molecule or driven by another source of energy, such as ATP hydrolysis or the electrochemical gradient of another moving molecule. Based on these two groups we can classify transport membrane proteins as channels/uniporters and active transporters: pumps, symporters or antiporters.
One important function of some of these membrane proteins is the creation and dissipation of ion gradients. For example, the plasma membrane Ca2+ ATPase transports calcium ions upon ATP hydrolysis and creates a gradient across the membrane; calcium channels, on the other hand, let calcium ions move down their electrochemical gradient resulting in its dissipation. The interplay between many different ion transport proteins leads to the generation of electrical impulses in neurons and muscle; moreover, ion gradients serve as stores of metabolic energy. Ultimately, the activity of these membrane proteins underlies phenomena such as heartbeat, sensation and thought and a complete understanding of cellular and organism physiology depends on our knowledge of these transport processes at the molecular level.
Our ultimate aim is to define the molecular mechanisms of transport and regulation of ion transport proteins. We use a combination of X-ray crystallography and biophysical/biochemical approaches.
Selected Publications
Morais Cabral, J. H., Zhou, Y. and Mackinnon, R. Energetic optimization of ion conduction rate by the K+ selectivity filter. Nature 414, 37-42 (2001)
Zhou, M., Morais Cabral, J. H. and Mann, S., Mackinnon, R. Potassium channel receptor site for the inactivation gate and quaternary amine inhibitors. Nature, 411, 657-661 (2001)
Zhou, Y., Morais Cabral, J. H. ,Kaufman, A. and Mackinnon, R. Chemistry of ion hydration and coordination revealed by a K+ channel-Fab complex structure. Nature 414, 43-48 (2001)
Clayton, G., Silverman, W., Heginbotham, L. and Morais Cabral, J. H. Structural basis of activation of a bacterial cyclic nucleotide regulated potassium channel. Cell 119, 615-627 (2004)
Albright, R. A., Vazquez Ibar, J.-L., Kim, C. U., Gruner, S. M. and Morais Cabral, J. H. The RCK domain of the KtrAB K+ transporter: multiple conformations of an octameric ring. Cell 126, 1147-1159 (2006)
Last Updated 12-18-06
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