Molecular biology of membrane proteins

Our lab concentrates on the study of membrane-proteinsWe study the molecular mechanisms involved in transport and energy transduction. The five main subjects that we are currently engaged in are:

1. Structure, function and molecular biology of photosystem I and other membrane complexes in higher plant chloroplasts. We solve the structure of plant PSI super-complex including its four light-harvesting complexes at 3.4 Å resolution.
2. Biochemistry and molecular biology of neurotransmitter transporters. Some of the neurotransmitter transporters that we study have been implicated in epilepsy, drug addiction, depression and several other neurological diseases. We aim at the elucidation of their structure.
3. Function of metal-ion transporters which are involved in resistance or sensitivity of mammalian cells to microorganisms. We have proposed that a family of metal-ion transporters, discovered in our laboratory, can be targeted in the aim of developing new concepts for counteracting bacterial infection, as well as for treatments of hereditary disorders.
4. The biology of Vacuolar H+-ATPase (V-ATPase) in yeast, plants and mammalian cells which is vital for every eukaryotic cell and functions in numerous processes including pH regulation in the kidney and bone resorption by osteoclasts. We solved the structure of V-ATPase subunit C at 1.75 Å resolution and aim at solving the structure of several other subunits of this important complex.
5. We invented heterologous expression system of eukaryotic membrane proteins in E. coli and aim at solving the structure of the expressed proteins.

The common denominator to all these subjects is the use of recombinant DNA technology, biochemistry, structural biology and genetics to unravel the structure and function of membrane proteins.

1. Nelson, H. and Nelson, N. (1990) Disruption of genes encoding subunits of yeast vacuolar H+-ATPase causes conditional lethality. Proc. Natl. Acad.
   Sci. USA 87: 3503-3507. (pdf)
2. Nelson, H., Mandiyan, S. and Nelson , N. (1990) Cloning of the human brain GABA transporter. FEBS Lett. 269: 181-184.
3. Nelson, N. (1991) Structure and pharmacology of the proton-ATPases. TIPS 12: 71-75.
4. Nelson, N. (1992) Evolution of organellar proton-ATPases. Biochim. Biophys. Acta 1100: 109-124.
5. Bü ttner, M., Xie, D.-L., Nelson, H., Pinther, W., Hauska, G. and Nelson, N. (1992) Photosynthetic reaction center genes in green sulfur bacteria and in Photosystem I are related. Proc. Natl. Acad. Sci. USA 89: 8135-8139. (pdf)
6. Liu, Q.-R., Mandiyan, S., Nelson, H. and Nelson, N. (1992) A family of genes encoding neurotransmitter transporters. Proc. Natl. Acad. Sci. USA (pdf)
   89: 6639-6643.
7. Liu, Q.-R., López-Corcuera, B., Nelson, H., Mandiyan, S. and Nelson, N. (1992) Cloning and expression of a cDNA encoding the transporter of taurine and -alanine in mouse brain. Proc. Natl. Acad. Sci. USA 89: 12145-12149. (pdf)
8. Liu, Q.-R., Ló pez-Corcuera, B., Mandiyan, S., Nelson, H. and Nelson, N. (1993) Molecular characterization of four pharmacologically distinct GABA transporters in mouse brain. J. Biol. Chem. 268: 2106-2112. (pdf)
9. Liu, Q.-R., Ló pez-Corcuera, B., Mandiyan, S., Nelson, H. and Nelson, N. (1993) Cloning and expression of a spinal cord and brain-specific glycine transporter with novel structural features. J. Biol. Chem. 268: 22802-22808. (pdf)
10. Supek, F., Supekova, L. and Nelson, N. (1994) Features of vacuolar H+-ATPase revealed by yeast suppressor mutants. J. Biol. Chem. 269: 26479-26485. (pdf)
11. Jursky, F. and Nelson, N. (1995) Localization of glycine neurotransmitter transporter (GLYT2) reveals correlation with the distribution of glycine receptor. J. Neuro. Chem. 64: 1026-1033. (pdf)
12. Nelson, H., Mandiyan, S. and Nelson, N. (1995) A bovine cDNA and a yeast gene-VMA8 encoding subunit D of the vacuolar H+-ATPase. Proc. Natl. Acad. Sci. USA 92: Proc. Natl. Acad. Sci. USA 92: 497-501. (pdf)
13. Tamura, S., Nelson, H., Tamura, A. and Nelson, N. (1995) Short external loops as potential substrate binding sites of GABA transporters. J. Biol. Chem. 270: 28712-28715. (pdf)
14. Supek, F., Supekova, L., Nelson, H. and Nelson, N. (1996) A yeast manganese transporter related to the macrophage protein involved in conferring resistance to mycobacteria. Proc. Natl. Acad. Sci. USA 93: 5105-5110. (pdf)
15. Supek, F., Supekova, L., Nelson, H. and Nelson, N. (1997) Function of metal-ion homeostasis in cell divison cycle, mitochondrial protein processing, sensitivity to mycobacterial infection and brain functions. J. Exp. Biol. 200: 321-330. (pdf)
16. Orgad S., Nelson, H., Segal, D. and Nelson, N. (1998) Metal ions suppress the abnormal taste behavior of the Drosophila mutant malvolio. J. Exp. Biol. 201: 115-120. (pdf)
17. Nelson, N. (1998) The family of Na+/Cl- neurotransmitter transporters. J. Neurochem. 71: 1785-1803. (pdf)
18. Nelson, N. and Harvey, W.R. (1999) Vacuolar and plasma membrane V-ATPases. Phys. Rev. 79: 361-385. (pdf)
19. Nelson, N. (1999). Metal-ion transporters and homeostasis. EMBO J. 18: 4361-4371. (pdf)
20. Cohen, A., Perzov, N., Nelson, H. and Nelson, N. (1999). A novel family of yeast chaperons involved in the distribution of V-ATPase and other membrane proteins. J. Biol Chem. 274: 26885-26893. (pdf)
21. Grossman, T.R., Luque, J.M. and Nelson, N. (2000). Identificatioin of a ubiquitous family of membrane proteins and their expression in mouse brain. J. Exp. Biol. 203: 447-457. (pdf)
22. Cohen, A., Nelson, H. and Nelson, N. (2000). The family of SMF metal-ion transporters in yeast cells. J. Biol. Chem. 275: 33388-33394. (pdf)
23. Perzov, N., Nelson, H. and Nelson, N. (2000). Altered distribution of the yeast plasma membrane H+-ATPase as a feature of vacuolar H+-ATPase null mutants. J. Biol. Chem. 275: 40088-40095. (pdf)
24. Nelson, N. and Ben-Shem, A. (2002). Photosystem I reaction center: Past and future . Photosyth. Res. 73: 193-206 (pdf)
25. Nelson, N., Sacher, A. and Nelson, H. (2002) The significance of molecular slips in transport systems. Nat. Rev. Mol. Cell Biol. 3: 876-881 (pdf)
26. Cohen, A., Nevo, Y. and Nelson, N. (2003). The first external loop of the metal-ion transporter DCT1 is involved in metal-ion binding and specificity. Proc. Natl. Acad. Sci. USA 100, 10694-10699 (pdf)
27. Ben-Shem, A. Frolow, F. and Nelson, N. (2003). The crystal structure of plant photosystem I. Nature 426, 630-635 (pdf)
28. Ben-Shem, A. Frolow, F. and Nelson, N. (2004). Evolution of Photosystem I – from Symmetry through Pseudosymmetry to Assymmetry. FEBS Lett. 564, 274-280 (pdf)
29. Nelson, N. and Ben-Shem, A. (2004). The complex architecture of oxygenic photosynthesis. Nat. Rev. Mol. Cell Biol. 5, 971-982 (pdf)
30. Drory, O., Frolow, F. and Nelson, N. (2004). Crystal structure of yeast V-ATPase subunit C reveals its stator function. EMBO Rep. 5, 1148-1152 (pdf)
31. Nevo, Y. and Nelson, N. (2004). The Mutation F227I Increases the Coupling of Metal Ion Transport in DCT1. J. Biol. Chem. 279, 53056-53061 (pdf)
32. Cohen-Kfir, E., Lee, W., Eskandari, S. and Nelson, N. (2005). Zinc Inhibition of the -Aminobutyric Acid Transporter-4 (GAT4) Reveals a Novel Link between Excitatory and Inhibitory Neurotransmission. Proc. Natl. Acad. Sci. USA 102, 6154-6159 (pdf)
33. Junge, W. and Nelson, N. (2005). Nature's rotary electromotors. Science 308, 642-644 (pdf)
34. Nelson, N. and Ben-Shem, A. (2005). The structure of photosystem I and evolution of photosynthesis. BioEssays 27, 914-922. (pdf)
35. Nelson, N. and Yocum, C. (2006). Structure and Function of Photosystems I and II. Annu. Rev. Plant Biol. 57, 521-565. (pdf)
36. Amunts, A., Drory, O. and Nelson, N. (2007). The structure of a plant photosystem I supercomplex at 3.4 Å resolution. Nature 447, 58-63. (pdf)