Research Interests
Almost 30 % of all genomes sequenced to date encode membrane proteins. These play vital roles in many areas of cell biology such as signalling, the selective uptake or removal of molecules from the cell and the maintenance of cellular pH or ion concentration. Despite their importance in physiology and drug discovery there is a relative paucity in the number of structures solved. The goal of my research is in understanding the structure and mechanism of these dynamic proteins through the use of X-ray crystallography in combination with other biochemical and biophysical techniques.
In particular my group is focussed on secondary active transporters. These proteins harness electrochemical gradients to transport ions or molecules across membranes.
We have solved the structure of a number of transporters and are probing their mechanisms through a combination of X-ray crystallography, biochemistry, site-directed mutagenesis, chemistry and computational chemistry.
Biography
DPhil, Chemistry. University of York, 1993
BSc Biophysics. University of Leeds 1989
- 'Brotherton, Deborah H., 'Savva, Christos G., 'Ragan, Timothy J., 'Dale, Nicholas, 'Cameron, Alexander D., 2022. 'Conformational changes and CO2-induced channel gating in connexin26. Structure, 30 (5), pp. 697-706.e4
- 'Hatton, Caitlin, 'Brotherton, Deborah H., 'Spencer, Mahalah, 'Cameron, Alexander D., 2022. 'Structure of cytosine transport protein CodB provides insight into nucleobase?cation symporter 1 mechanism. The EMBO Journal, 41 (16)
- Furze, Christopher M., Delso, Ignacio, Casal, Enriqueta, Guy, Collette S., Seddon, Chloe, Brown, Chelsea M., Parker, Hadyn L., Radhakrishnan, Anjana, Pacheco-Gomez, Raul, Stansfeld, Phillip J., Angulo, Jesus, Cameron, Alexander D., Fullam, Elizabeth, 2021. Structural basis of trehalose recognition by the mycobacterial LpqY-SugABC transporter. Journal of Biological Chemistry, 296
- Quareshy, Mussa, Shanmugam, Muralidharan, Townsend, Eleanor, Jameson, Eleanor, Bugg, Timothy D. H., Cameron, Alexander, Chen, Yin, 2021. Structural basis of carnitine monooxygenase CntA substrate specificity, inhibition and inter-subunit electron transfer. Journal of Biological Chemistry, 296
- Saouros, Savvas, Mohan, Thotegowdanapalya C., Cecchetti, Cristina, Lehmann, Silke, Barritt, Joseph D., Scull, Nicola J., Simpson, Paul, Alguel, Yilmaz, Cameron, Alexander D., Jones, Alexandra M. E., Byrne, Bernadette, 2021. Structural and functional insights into the mechanism of action of plant borate transporters. Scientific Reports, 11 (1)
- Shanmugam, Muralidharan, Quareshy, Mussa, Cameron, Alexander, Bugg, Timothy D. H., Chen, Yin, 2021. Light-activated electron transfer and catalytic mechanism of carnitine oxidation by Rieske-type oxygenase from human microbiota. Angewandte Chemie International Edition, 60 (9), pp. 4529-4534
- Cecchetti, Cristina, Scull, Nicola J., Mohan, Thotegowdanapalya C., Alguel, Yilmaz, Jones, Alexandra M. C., Cameron, Alexander D., Byrne, Bernadette, 2021. Transfer of stabilising mutations between different secondary active transporter families. FEBS Open Bio, 11 (6), pp. 1685-1694
- Saouros, Savvas, Cecchetti, Cristina, Jones, Alexandra M., Cameron, Alexander, Byrne, Bernadette, 2020. Strategies for successful isolation of a eukaryotic transporter. Protein Expression and Purification, 166
- Jacomin, Anne-Claire, Petridi, Stavroula, Di Monaco, Marisa, Bhujabal, Zambarlal, Jain, Ashish, Mulakkal, Nitha Charles, Palara, Anthimi, Powell, Emma L., Chung, Bonita, Zampronio, Cleidiane, Jones, Alexandra M., Cameron, Alexander, Johansen, Terje, Nezis, Ioannis P., 2020. Regulation of expression of autophagy genes by Atg8a-interacting partners Sequoia, YL-1 and Sir2 in Drosophila. Cell Reports, 31 (8)
- Santos Rodrigues, Fabio Henrique dos, Firczuk, Helena, Breeze, Alexander L., Cameron, Alexander, Walko, Martin, Wilson, Andrew J, Zanchin , Nilson I.T., McCarthy, John E. G., 2019. The Leishmania PABP1?eIF4E4 interface : a novel 5'?3' interaction architecture for trans-spliced mRNAs. Nucleic Acids Research, 47 (3), pp. 1493-1504
- Fenn, Jonathan S., Nepravishta, Ridvan, Guy, Collette S., Harrison, James, Angulo, Jesus, Cameron, Alexander, Fullam, Elizabeth, 2019. Structural basis of glycerophosphodiester recognition by the mycobacterium tuberculosis substrate-binding protein UgpB. ACS Chemical Biology, 14 (9), pp. 1879-1887
- Morris, Kyle L., Jones, Joseph Reuben, Halebian, Mary, Wu, Shenping, Baker, Michael, Armache, Jean-Paul, Avila Ibarra, Amaurys, Sessions, Richard B., Cameron, Alexander, Cheng, Yifan, Smith, Corinne J., 2019. Cryo-EM of multiple cage architectures reveals a universal mode of clathrin self assembly. Nature Structural & Molecular Biology, 26, pp. 890-898
- Ahangar, Mohd Syed, Furze, Christopher M., Guy, Collette S., Cooper, Charlotte, Maskew, Kathryn S, Graham, Ben, Cameron, Alexander, Fullam, Elizabeth, 2018. Structural and functional determination of homologs of the Mycobacterium tuberculosis N-acetylglucosamine-6-phosphate deacetylase (NagA). Journal of Biological Chemistry, 293 (25), pp. 9770-9783
- Alguel, Yilmaz, Amillis, Sotiris, Leung, James, Lambrinidis, George, Capaldi, Stefano, Scull, Nicola J., Craven, Gregory, Iwata, So, Armstrong, Alan, Mikros, Emmanuel, Diallinas, George, Cameron, Alexander, Byrne, Bernadette, 2016. Structure of eukaryotic purine/H+ symporter UapA suggests a role for homodimerization in transport activity. Nature Communications, 7, pp. 1-9
- Coincon, Mathieu, Uzdavinys, Povilas, Nji, Emmanuel, Dotson, David L., Winkelmann, Iven, Abdul-Hussein, Saba, Cameron, Alexander, Beckstein, Oliver, Drew, David, 2016. Crystal structures reveal the molecular basis of ion translocation in sodium/proton antiporters. Nature Structural & Molecular Biology, 23 (3), pp. 248-255
- Alguel, Y., Cameron, Alexander, Diallinas, G., Byrne, B., 2016. Transporter oligomerization : form and function. Biochemical Society Transactions, 44 (6), pp. 1737-1744
- Arakawa, Takatoshi, Kobayashi-Yurugi, Takami, Alguel, Yilmaz, Iwanari, Hiroko, Hatae, Hinako, Iwata, Momi, Abe, Yoshito, Hino, Tomoya, Ikeda-Suno, Chiyo, Kuma, Hiroyuki, Kang, Dongchon, Murata, Takeshi, Hamakubo, Takao, Cameron, Alexander, Kobayashi, Takuya, Hamasaki, Naotaka, Iwata, So, 2015. Crystal structure of the anion exchanger domain of human erythrocyte band 3. Science, 350 (6261), pp. 680-684
- Simmons, Katie J., Jackson, Scott M., Brueckner, Florian, Patching, Simon G., Beckstein, Oliver, Ivanova, Ekaterina, Geng, Tian, Weyand, Simone, Drew, David, Lanigan, Joseph, Sharples, David J., Sansom, M. S. P. (Mark S. P.), Iwata, So, Fishwick, Colin W. G., Johnson, A. Peter, Cameron, Alexander, Henderson, P. J. F. (Peter J. F.), 2014. Molecular mechanism of ligand recognition by membrane transport protein, Mhp1. The EMBO Journal, 33 (16), pp. 1831-1844
- Lee, Chiara, Yashiro, Shoko, Dotson, David L., Uzdavinys, Povilas, Iwata, So, Sansom, Mark S. P., von Ballmoos, Christoph, Beckstein, Oliver, Drew, David, Cameron, Alexander, 2014. Crystal structure of the sodium-proton antiporter NhaA dimer and new mechanistic insights. The Journal of General Physiology, 144 (6), pp. 529-544
- Lee, Chiara, Kang, Hae Joo, von Ballmoos, Christoph, Newstead, Simon, Uzdavinys, Povilas, Dotson, David L., Iwata, So, Beckstein, Oliver, Cameron, Alexander, Drew, David, 2013. A two-domain elevator mechanism for sodium/proton antiport. Nature, 501 (7468), pp. 573-577
- Leung, James, Cameron, Alexander, Diallinas, George, Byrne, Bernadette, 2013. Stabilizing the heterologously expressed uric acid-xanthine transporter UapA from the lower eukaryoteAspergillus nidulans. Molecular Membrane Biology, 30 (1), pp. 32-42
- Foadi, James, Aller, Pierre, Alguel, Yilmaz, Cameron, Alexander, Axford, Danny, Owen, Robin L., Armour, Wes, Waterman, David G., Iwata, So, Evans, Gwyndaf, 2013. Clustering procedures for the optimal selection of data sets from multiple crystals in macromolecular crystallography. Acta Crystallographica Section D Biological Crystallography, 69 (8), pp. 1617-1632
- Solcan, Nicolae, Kwok, Jane, Fowler, Philip W, Cameron, Alexander, Drew, David, Iwata, So, Newstead, Simon, 2012. Alternating access mechanism in the POT family of oligopeptide transporters. The EMBO Journal, Vol. 31 (No. 16), pp. 3411-3421
- Iwata, M., Lee, Y., Yamashita, T., Yagi, T., Iwata, So, Cameron, Alexander, Maher, M. J., 2012. The structure of the yeast NADH dehydrogenase (Ndi1) reveals overlapping binding sites for water- and lipid-soluble substrates. Proceedings of the National Academy of Sciences, Vol. 109 (No. 38), pp. 15247-15252
- Hino, Tomoya, Arakawa, Takatoshi, Iwanari, Hiroko, Yurugi-Kobayashi, Takami, Ikeda-Suno, Chiyo, Nakada-Nakura, Yoshiko, Kusano-Arai, Osamu, Weyand, Simone, Shimamura, Tatsuro, Nomura, Norimichi, Cameron, Alexander, Kobayashi, Takuya, Hamakubo, Takao, Iwata, So, Murata, Takeshi, 2012. G-protein-coupled receptor inactivation by an allosteric inverse-agonist antibody. Nature, Vol. 482, pp. 237-240
- Newstead, Simon, Drew, David, Cameron, Alexander, Postis, Vincent L. G., Xia, Xiaobing, Fowler, Philip W., Ingram, Jean C., Carpenter, Elisabeth P., Sansom, M. S. P. (Mark S. P.), McPherson, Michael J., Baldwin, Stephen A., Iwata, So, 2011. Crystal structure of a prokaryotic homologue of the mammalian oligopeptide?proton symporters, PepT1 and PepT2. The EMBO Journal, Vol. 30 (No. 2), pp. 417-426
- Ito, Keisuke, Ito, Sohei, Shimamura, Tatsuro, Weyand, Simone, Kawarasaki, Yasuaki, Misaka, Takumi, Abe, Keiko, Kobayashi, Takuya, Cameron, Alexander, Iwata, So, 2011. Crystal Structure of Glucansucrase from the Dental Caries Pathogen Streptococcus mutans. Journal of Molecular Biology, Vol. 408 (No. 2), pp. 177-186
- Weyand, Simone, Shimamura, Tatsuro, Beckstein, Oliver, Sansom, M. S. P. (Mark S. P.), Iwata, So, Henderson, P. J. F. (Peter J. F.), Cameron, Alexander, 2011. The alternating access mechanism of transport as observed in the sodium-hydantoin transporter Mhp1. Journal of Synchrotron Radiation, Vol. 18 (No. 1), pp. 20-23
- Choudhury, Hassanul G., Cameron, Alexander, Iwata, So, Beis, Konstantinos, 2011. Structure and mechanism of the chalcogen-detoxifying protein TehB fromEscherichia coli. Biochemical Journal, Vol. 435 (No. 1), pp. 85-91
- Hu, Nien-Jen, Iwata, So, Cameron, Alexander, Drew, David, 2011. Crystal structure of a bacterial homologue of the bile acid sodium symporter ASBT. Nature, Vol. 478 (No. 7369), pp. 408-411
- Sonoda, Yo, Newstead, Simon, Hu, Nien-Jen, Alguel, Yilmaz, Nji, Emmanuel, Beis, Konstantinos, Yashiro, Shoko, Lee, Chiara, Leung, James, Cameron, Alexander, Byrne, Bernadette, Iwata, So, Drew, David, 2011. Benchmarking Membrane Protein Detergent Stability for Improving Throughput of High-Resolution X-ray Structures. Structure, Vol. 19 (No. 1), pp. 17-25
- Shimamura, Tatsuro, Weyand, Simone, Beckstein, Oliver, Rutherford, N. G., Hadden, J. M., Sharples, D., Sansom, M. S. P. (Mark S. P.), Iwata, So, Henderson, P. J. F. (Peter J. F.), Cameron, Alexander, 2010. Molecular Basis of Alternating Access Membrane Transport by the Sodium-Hydantoin Transporter Mhp1. Science, Vol. 328 (No. 5977), pp. 470-473
- Sonoda, Yo, Cameron, Alexander, Newstead, Simon, Omote, Hiroshi, Moriyama, Yoshinori, Kasahara, Michihiro, Iwata, So, Drew, David, 2010. Tricks of the trade used to accelerate high-resolution structure determination of membrane proteins. FEBS Letters, Vol. 584 (No. 12), pp. 2539-2547
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Bindi, Simona, Fancelli, Daniele, Alli, Cristina, Berta, Daniela, Bertrand, Jay A., Cameron, Alexander, Cappella, Paolo, Carpinelli, Patrizia, Cervi, Giovanni, Croci, Valter, D'Anello, Matteo, Forte, Barbara, Laura Giorgini, M., Marsiglio, Aurelio, Moll, Juergen, Pesenti, Enrico, Pittalà, Valeria, Pulici, Maurizio, Riccardi-Sirtori, Federico, Roletto, Fulvia et al (Select to open full list), 2010. Thieno[3,2-c]pyrazoles: A novel class of Aurora inhibitors with favorable antitumor activity. Bioorganic & Medicinal Chemistry, Vol. 18 (No. 19), pp. 7113-7120
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Brasca, Maria Gabriella, Amboldi, Nadia, Ballinari, Dario, Cameron, Alexander, Casale, Elena, Cervi, Giovanni, Colombo, Maristella, Colotta, Francesco, Croci, Valter, D'Alessio, Roberto, Fiorentini, Francesco, Isacchi, Antonella, Mercurio, Ciro, Moretti, Walter, Panzeri, Achille, Pastori, Wilma, Pevarello, Paolo, Quartieri, Francesca, Roletto, Fulvia, Traquandi, Gabriella et al (Select to open full list), 2009. Identification ofN,1,4,4-Tetramethyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (PHA-848125), a Potent, Orally Available Cyclin Dependent Kinase Inhibitor. Journal of Medicinal Chemistry, Vol. 52 (No. 16), pp. 5152-5163
- Carpenter, Elisabeth P, Beis, Konstantinos, Cameron, Alexander, Iwata, So, 2008. Overcoming the challenges of membrane protein crystallography. Current Opinion in Structural Biology, Vol. 18 (No. 5), pp. 581-586
- Weyand, Simone, Shimamura, Tatsuro, Yajima, S., Suzuki, S., Mirza, O., Krusong, K., Carpenter, E. P., Rutherford, N. G., Hadden, J. M., O'Reilly, J., Ma, P., Saidijam, M., Patching, S. G., Hope, R. J., Norbertczak, H. T., Roach, P. C. J., Iwata, So, Henderson, P. J. F. (Peter J. F.), Cameron, Alexander, 2008. Structure and Molecular Mechanism of a Nucleobase-Cation-Symport-1 Family Transporter. Science, Vol. 322 (No. 5902), pp. 709-713
- Hu, Nien-Jen, Rada, Heather, Rahman, Nahid, Nettleship, Joanne E., Bird, Louise, Iwata, So, Drew, David, Cameron, Alexander, Owens, Raymond J., 2014. GFP-Based expression screening of membrane proteins in insect cells using the baculovirus system. In Owens, Raymond J. (ed.), Structural Proteomics : High-Throughput Methods, Humana Press, pp. 197-209
- Saouros, Savvas, Mohan, Thotegowdanapalya C., Cecchetti, Cristina, Lehmann, Silke, Barritt, Joseph D., Scull, Nicola J., Simpson, Paul, Alguel, Yilmaz, Cameron, Alexander D., Jones, Alexandra M. E., Byrne, Bernadette, 2020. Structural and functional insights into the mechanism of action of plant boron transporters [pre-print]. bioRxiv
| Title | Funder | Award start | Award end |
|---|---|---|---|
| BBSRC Mid-range Equipment ALERT 2021 Application - November 2021 | BBSRC | 01 Aug 2022 | 31 Jul 2023 |
| Structural and functional characterization of the major auxin uptake carrier AUX1 protein (Chitra Joshi) | Medical and Life Sciences Research Fund | 01 Aug 2021 | 31 Mar 2022 |
| Structural and biophysical basis of Connexin26 channel mediated disease | MRC | 01 Jan 2017 | 31 Dec 2021 |
| H20 MC: Crystal structures of PIN proteins - CrysPINs. MSCA IF EF ST for Fellow Martin Kubes | European Commission | 01 Aug 2018 | 31 Jul 2020 |
| Biochemical and structural characterisation of a unique Rieske oxygenase CntA - FULL RPG application | Leverhulme Trust | 08 May 2017 | 31 Jul 2020 |
| Elucidating molecular level details of the plant Borate transporter structure and function | BBSRC | 03 Oct 2016 | 31 Mar 2020 |
| In-depth structural characterization of the tetraspanin CD81 | BBSRC | 01 Apr 2016 | 31 Mar 2019 |
| Structural basis of the CO2 sensitivity of Cx26 and role in human physiology | Leverhulme Trust | 01 Jul 2015 | 31 Mar 2018 |
| Subproject for Institution # 39462 | BBSRC | 01 Oct 2014 | 31 Jan 2018 |
| Trypanosomatid protein synthesis as a target for novel drug therapies | MRC | 01 Jan 2016 | 31 Dec 2017 |
| Subcontract for BB/K017292/1 from Imperial | BBSRC | 01 Jul 2013 | 30 Jun 2016 |