ARKIN, ISAIAH

Born 1965, Petach-Tikva (Israel).
Ph.D. 1996, Yale University; Lecturer, CambridgeUniversity 1997; Senior Lecturer, Hebrew University 2000.

E-mail: arkin@cc.huji.ac.il

Tel: 972 (0)2-658-4329; Fax: 972 (0)2-658-4329

Research Interests:

Computational (bioinformatics) and experimental structural biology of membrane proteins: use and development of novel experimental and computational approaches to elucidate membrane proteins structure. The focus of my group is structural biology of membrane proteins, due to the following 3 reasons: (I) Membrane proteins are by far the most bio-medically important family of proteins, serving as the targets for the vast majority of pharmaceutical agents. (II) Membrane proteins are exceptionally abundant in all genomes sequences so far, encompassing 20-30% of the proteome. (III) Regrettably, membrane proteins are dramatically underrepresented in the protein data bank, more than 2 orders of magnitude less abundant relative to water-soluble proteins.

Research Highlights:

1. Using FTIR spectroscopy, we have invented a novel method to determine precise backbone structures of membrane proteins in a lipid bilayer and applied it to several pharmaceutically important viral ion channels.

2. Using bioinformatics tools, we were able to show that the underlying paradigm for membrane proteins: ``Membrane proteins are inside-out proteins'' is simply incorrect.

3. Bioinformatics analysis pointed out the potential problems in whole genome analysis of membrane proteins due to AT/GC bias effects.

4. Analysis of the abundance of membrane proteins in nearly two-dozen proteomes was investigated using optimized hydropathy analysis. The results of this bioinformatics analysis indicated that more complex organisms do not posses a higher complement of membrane proteins, as previously expected.

5. Guided by evolutionary conservation data from multiple genomes, and molecular dynamics simulations we obtained a model for the bacterial multi-drug H+ anti-porter, EmrE.

6. We have recently developed an entirely different, and more rigorous approach to make use of evolutionary conservation data in membrane proteins modeling based on silent amino-acid substitutions. In this way one can tap into the plethora of data generated from genome sequencing efforts and to reliably generate models for membrane proteins. This approach is widely applicable and has an extensive potential usage.

Projects and studentships:

Please contact me for details, as I am always looking for help

Recent Publications (since 1995):

Arkin, I.T., Adams, P.D., MacKenzie, K.R., Lemmon, M.A., Brunger A.T. and Engelman, D.M. (1994) Structural organization of the pentameric transmembrane a-helices of phospholamban, a cardiac ion channel EMBO J. 13:4757-4764.

Adams, P.D., Arkin, I.T., Engelman, D.M. and Br?nger A.T. (1995) Computational searching and mutagenesis suggest a structure for the pentameric transmembrane domain of phospholamban. Nature Struct. Biol. 2:154-159.

Arkin, I.T., Russ, W.P., Lebendiker, M. and Schuldiner, S. (1996) Determining the secondary structure and orientation of EmrE, a multi-drug transporter, indicates a transmembrane four helix bundle. Biochem. 35:7233-7238.

Peled-Zehavi, H., Arkin, I.T., Engelman, D.M. and Shai, Y. (1996) Coassembly of synthetic segments of shaker K+ channel within phospholipid membranes. Biochem. 35:6828 -6838.

Ludlam, C.F.C., Arkin. I.T., Liu, X., Rothman, M.S., Rath, P., Aimoto, S., Smith, S.O., Engelman, D.M. and Rothschild K.J. (1996) FTIR spectroscopy and site-directed isotope labeling as a probe of local secondary structure in the transmembrane domain of phospholamban. Biophys. J. 70:1728-1736.

Arkin, I.T., MacKenzie, K.R., Fisher, L., Aimoto, S., Engelman, D.M. and Smith, S.O. (1996) Mapping the lipid exposed surfaces of membrane proteins. Nature Struct. Biol. 3:240 -243.

Arkin, I.T., MacKenzie, K.R. and Br?nger, A.T. (1997) Site directed dichroism as a method for obtaining rotational and orientational constraints for oriented polymers. J. Amer. Chem. Soc. 119:8973-8980.

Arkin, I.T., Br?nger, A.T. and Engelman, D.M. (1997) Are there dominant membrane protein families with a given number of helices? Prot. Struct. Func. Gen. 28:465-466

Lemmon, M.A., MacKenzie, K.R., Arkin, I.T. and Engelman, D.M. (1997) Transmembrane a-helix interactions in folding and oligomerization of integral membrane proteins. in Membrane protein assembly G. von Heijne (ed.) Springer New York.

Arkin, I.T., Adams. P.D., Br?nger, A.T, Smith, S.O. and Engelman, D.M. (1997) Structural perspectives of phospholamban, a helical transmembrane pentamer. Annu. Rev. Biophys. Biomol. Struct. 26:157-179.

Arkin, I.T., Adams. P.D., Aimoto, S., Br?nger, A.T., Engelman, D.M. and Smith, S.O. (1997) Structure of the transmembrane cysteine residues in the phospholamban ion channel. J. Membr. Biol. 155:199-206.

Arkin, I.T. and Br?nger, A.T. (1998) Statistical Analysis of Predicted Transmembrane a-Helices. Biochem. Biophys. Acta 1429:113-128.

Arkin, I.T., Sukharev, S.I., Blount, P., Kung, C. and Br?nger, A.T. (1998) Helicity, membrane incorporation, orientation and thermal stability of the large conductance mechanosensitive ion channel from E. coli. Biochem. Biophys. Acta 1369:131-140.

Kukol, A. and Arkin, I.T. (1999) Structure of the HIV-1 Vpu transmembrane complex determined by site-specific FTIR dichroism and global molecular dynamics searching. Biophys J. 77:1594-1601.

Stevens, T.J. and Arkin, I.T. (1999) Are membrane proteins ``inside-out'' proteins? Prot. Struct. Func. Gen. 36:135-143.

Kukol, A., Adams, P.D., Rice, L.M., Br?nger, A.T. and Arkin, I.T. (1999) Experimentally based orientational refinement of membrane protein models: A structure for the Influenza A M2 H+ channel. J. Mol. Biol. 286:951 -962.

Stevens, T.J. and Arkin, I.T. (2000) Genomic AT bias and transmembrane hydrophobicity. Proteins Science. 9:505-511.

Kukol, A. and Arkin, I.T. (2000) Structure of the Influenza C CM2 protein transmembrane domain obtained by site-specific infrared dichroism and global molecular dynamics searching. J. Biol. Chem. 275:4225-4229.

Forrest, L.R., Kukol, A., Arkin, I.T., Tieleman, D.P. and Sansom, M.S.P. (2000) Exploring models of the Influenza A M2 channel - MD simulation in phospholipid bilayer. Biophys J. 78:55-69.

Torres, J. and Arkin, I.T. (2000) Recursive use of evolutionary conservation data in molecular modeling of membrane proteins: A model of the multidrug H+ antiporter EmrE. Eur. J. Biochem. 267:3422-3431.

Stevens, T.J. and Arkin, I.T. (2000) Do more complex organisms have a greater proportion of membrane proteins? Proteins Struct Func Gen. 39:417-420.

Stevens, T.J. and Arkin, I.T. (2000) Turning an opinion ``inside-out'': Rees and Eisenberg's commentary (Prot. Struct. Func. Gen. 2000,38:121-2) on ``Are membrane proteins ``inside-out'' proteins?'' (Prot. Struct. Func. Gen. 1999,36:135-43). Prot. Struct. Func. Gen. 40:463-464.

Torres, J., Adams, P.D. and Arkin, I.T. (2000) Determination of the structure of phospholamban in a lipid bilayer. Spatial restraints resolve the ambiguity arising from interpretations of mutagenesis data. J. Mol. Biol. 300: 677-685.

The use of a single glycine residue to determine the tilt and orientation of a transmembrane helix. A new structural label for infrared spectroscopy. (2000) Torres, J., Kukol, A. and Arkin, I.T. Biophys J. 79:3139-3143.

Torres, J., Kukol, A. and Arkin, I.T. (2000) Mapping the energy surface of transmembrane helix-helix interactions. Biophys. J. in press.



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