Liz Carpenter

Principal Investigator

University of Oxford

I am the principal Investigator for the Integral Membrane Proteins group at the SGC. I am a structural biologist with extensive experience in X-ray crystallography of soluble proteins. I have a degree in Biochemistry from Cambridge University, UK, and a PhD from Birkbeck College, London. I was a post-doc in Paris and London, at the National Institute for Medical Research and at Imperial College, where I solved the structures of soluble proteins involved in DNA repair, toxoplasmosis and muscle movement. More recently I developed a fascination with the most challenging problems in structural biology, the structures and functions of proteins embedded in the membranes of cells. These proteins with large hydrophobic surfaces are particularly challenging to study and yet are essential for understanding the fundamental processes of movements of molecules and signals across cell membranes. In 2007 I moved to the Diamond Light Source in Oxfordshire to establish an international training facility, the Membrane Protein Laboratory. In 2009 I moved to the SGC to take charge of the Integral Membrane Proteins group.

Research Areas

My group has extensive experience in producing human membrane proteins from the Baculovirus/insect cell expression system. We have developed high throughput methods to rapidly screen constructs of membrane proteins, determine which length of protein is most stable, which detergents are suitable for protein production and which methods are optimum for protein purification. These methods allow us to purify a range of proteins for structure and function studies. We use enzyme assays, mass spectrometry and thermostability detection as tools to study the function of ABC transporters, enzymes and ion channels. For structural studies we use crystallisation in vapour phase and lipidic cubic phase and to determine structures we use X-ray crystallography. In the future we aim to improve methods for producing and stabilizing human membrane proteins, so that a broad range of IMP structures can be solved efficiently. We also plan in the future to develop small molecule binders, both activators and inhibitors, for human ion channels and other membrane proteins.

Publications

Structure of the polycystic kidney disease TRP channel Polycystin-2 (PC2).
Grieben, M; Pike, ACW; Shintre, CA; Venturi, E; El-Ajouz, S; Tessitore, A; Shrestha, L; Mukhopadhyay, S; Mahajan, P; Chalk, R; Burgess-Brown, NA; Sitsapesan, R; Huiskonen, JT; Carpenter, EP;
Nature Structural and Molecular Biology. 2017 24:114-122. doi: 10.1038/nsmb.3343
PMID: 27991905

An overview of heavy-atom derivatization of protein crystals.
Pike, ACW; Garman, EF; Krojer, T; von Delft, F; Carpenter, EP;
Acta Crystallographica. Section d, Structural Biology. 2016 72:303-318. doi: 10.1107/S2059798316000401
PMID: 26960118

Polymodal activation of the TREK-2 K2P channel produces structurally distinct open states.
McClenaghan, C; Schewe, M; Aryal, P; Carpenter, EP; Baukrowitz, T; Tucker, SJ;
Journal of General Physiology. 2016 147:497-505. doi: 10.1085/jgp.201611601
PMID: 27241700

Mammalian Glucose Transporter Activity Is Dependent upon Anionic and Conical Phospholipids.
Hresko, RC; Kraft, TE; Quigley, A; Carpenter, EP; Hruz, PW;
Journal of Biological Chemistry. 2016 291:17271-17282. doi: 10.1074/jbc.m116.730168
PMID: 27302065

ATP Binding and Hydrolysis Properties of ABCB10 and Their Regulation by Glutathione.
Qiu, W; Liesa, M; Carpenter, EP; Shirihai, OS;
PLoS ONE. 2015 10:e0129772-. doi: 10.1371/journal.pone.0129772
PMID: 26053025

K2P channel gating mechanisms revealed by structures of TREK-2 and a complex with Prozac.
Dong, YY; Pike, ACW; Mackenzie, A; McClenaghan, C; Aryal, P; Dong, L; Quigley, A; Grieben, M; Goubin, S; Mukhopadhyay, S; Ruda, GF; Clausen, MV; Cao, L; Brennan, PE; Burgess-Brown, NA; Sansom, MSP; Tucker, SJ; Carpenter, EP;
Science. 2015 347:1256-1259. doi: 10.1126/science.1261512
PMID: 25766236

Purification and interaction analyses of two human lysosomal vitamin B12 transporters: LMBD1 and ABCD4.
Deme, JC; Hancock, MA; Xia, X; Shintre, CA; Plesa, M; Kim, JC; Carpenter, EP; Rosenblatt, DS; Coulton, JW;
Molecular Membrane Biology. 2014 31:250-261. doi: 10.3109/09687688.2014.990998
PMID: 25535791

Structural basis for the recognition and cleavage of abasic DNA in Neisseria meningitidis.
Lu, D; Silhan, J; MacDonald, JT; Carpenter, EP; Jensen, K; Tang, CM; Baldwin, GS; Freemont, PS;
Proceedings of the National Academy of Sciences. 2012 109:16852-16857. doi: 10.1073/pnas.1206563109
PMID: 23035246

Crystal structure of a prokaryotic homologue of the mammalian oligopeptide-proton symporters, PepT1 and PepT2.
Newstead, S; Drew, D; Cameron, AD; Postis, VLG; Xia, X; Fowler, PW; Ingram, JC; Carpenter, EP; Sansom, MSP; McPherson, MJ; Baldwin, SA; Iwata, S;
EMBO Journal. 2011 30:417-426. doi: 10.1038/emboj.2010.309
PMID: 21131908

Insights into how nucleotide-binding domains power ABC transport.
Newstead, S; Fowler, PW; Bilton, P; Carpenter, EP; Sadler, PJ; Campopiano, DJ; Sansom, MSP; Iwata, S;
Structure. 2009 17:1213-1222. doi: 10.1016/j.str.2009.07.009
PMID: 19748342

Insights into outer membrane protein crystallization.
Newstead, S; Hobbs, J; Jordan, D; Carpenter, EP; Iwata, S;
Molecular Membrane Biology. 2008 25:631-638. doi: 10.1080/09687680802526574
PMID: 19023694

Structure and molecular mechanism of a nucleobase-cation-symport-1 family transporter.
Weyand, S; Shimamura, T; Yajima, S; Suzuki, S; Mirza, O; Krusong, K; Carpenter, EP; Rutherford, NG; Hadden, JM; O'Reilly, J; Ma, P; Saidijam, M; Patching, SG; Hope, RJ; Norbertczak, HT; Roach, PCJ; Iwata, S; Henderson, PJF; Cameron, AD;
Science. 2008 322:709-713. doi: 10.1126/science.1164440
PMID: 18927357

Overcoming the challenges of membrane protein crystallography.
Carpenter, EP; Beis, K; Cameron, AD; Iwata, S;
Current Opinion in Structural Biology. 2008 18:581-586. doi: 10.1016/j.sbi.2008.07.001
PMID: 18674618

2018

ZMPSTE24 missense mutations that cause progeroid diseases decrease prelamin A cleavage activity and/or protein stability.
Spear, ED; Hsu, E-T; Nie, L; Carpenter, EP; Hrycyna, CA; Michaelis, S;
Disease Models & Mechanisms. 2018 11:-. doi: 10.1242/dmm.033670
PMID: 29794150

2017

The SGC beyond structural genomics: redefining the role of 3D structures by coupling genomic stratification with fragment-based discovery.
Bradley, AR; Echalier, A; Fairhead, M; Strain-Damerell, C; Brennan, P; Bullock, AN; Burgess-Brown, NA; Carpenter, EP; Gileadi, O; Marsden, BD; Lee, WH; Yue, W; Bountra, C; von Delft, F;
Essays in Biochemistry. 2017 61:495-503. doi: 10.1042/EBC20170051
PMID: 29118096

Asymmetric mechanosensitivity in a eukaryotic ion channel.
Clausen, MV; Jarerattanachat, V; Carpenter, EP; Sansom, MSP; Tucker, SJ;
Proceedings of the National Academy of Sciences. 2017 114:E8343-E8351. doi: 10.1073/pnas.1708990114
PMID: 28923939

Regulation of Two-pore Domain K plus Channels by Natural Effectors and Pharmacological Agents
Schewe, M; Schulz, F; Mert, U; Sun, H; Belabed, H; Musinszki, M; Koehler, T; Tegtmeier, M; Nazare, M; Carpenter, EP; Tucker, SJ; Baukrowitz, T;
Acta Physiologica. 2017 :-. doi:
PMID:

Bilayer-Mediated Structural Transitions Control Mechanosensitivity of the TREK-2 K2P Channel.
Aryal, P; Jarerattanachat, V; Clausen, MV; Schewe, M; McClenaghan, C; Argent, L; Conrad, LJ; Dong, YY; Pike, ACW; Carpenter, EP; Baukrowitz, T; Sansom, MSP; Tucker, SJ;
Structure. 2017 25:708-718.e2. doi: 10.1016/j.str.2017.03.006
PMID: 28392258

Structural and Functional Response of a Mechanosensitive K2P K+ Channel to Asymmetric Membrane Tension
Jarerattanachat, V; Clausen, MV; Aryal, P; Carpenter, EP; Sansom, MSP; Tucker, SJ;
Biophysical Journal. 2017 :-. doi:
PMID:

Structure of the polycystic kidney disease TRP channel Polycystin-2 (PC2).
Grieben, M; Pike, ACW; Shintre, CA; Venturi, E; El-Ajouz, S; Tessitore, A; Shrestha, L; Mukhopadhyay, S; Mahajan, P; Chalk, R; Burgess-Brown, NA; Sitsapesan, R; Huiskonen, JT; Carpenter, EP;
Nature Structural and Molecular Biology. 2017 24:114-122. doi: 10.1038/nsmb.3343
PMID: 27991905

Molecular insights into lipid-assisted Ca2+ regulation of the TRP channel Polycystin-2.
Wilkes, M; Madej, MG; Kreuter, L; Rhinow, D; Heinz, V; De Sanctis, S; Ruppel, S; Richter, RM; Joos, F; Grieben, M; Pike, ACW; Huiskonen, JT; Carpenter, EP; Kühlbrandt, W; Witzgall, R; Ziegler, C;
Nature Structural and Molecular Biology. 2017 24:123-130. doi: 10.1038/nsmb.3357
PMID: 28092368

2016

Mass spectrometry captures off-target drug binding and provides mechanistic insights into the human metalloprotease ZMPSTE24.
Mehmood, S; Marcoux, J; Gault, J; Quigley, A; Michaelis, S; Young, SG; Carpenter, EP; Robinson, CV;
Nature Chemistry. 2016 8:1152-1158. doi: 10.1038/nchem.2591
PMID: 27874871

Mammalian Glucose Transporter Activity Is Dependent upon Anionic and Conical Phospholipids.
Hresko, RC; Kraft, TE; Quigley, A; Carpenter, EP; Hruz, PW;
Journal of Biological Chemistry. 2016 291:17271-17282. doi: 10.1074/jbc.m116.730168
PMID: 27302065

Polymodal activation of the TREK-2 K2P channel produces structurally distinct open states.
McClenaghan, C; Schewe, M; Aryal, P; Carpenter, EP; Baukrowitz, T; Tucker, SJ;
Journal of General Physiology. 2016 147:497-505. doi: 10.1085/jgp.201611601
PMID: 27241700

An overview of heavy-atom derivatization of protein crystals.
Pike, ACW; Garman, EF; Krojer, T; von Delft, F; Carpenter, EP;
Acta Crystallographica. Section d, Structural Biology. 2016 72:303-318. doi: 10.1107/S2059798316000401
PMID: 26960118

2015

Structures and functions of mitochondrial ABC transporters.
Schaedler, TA; Faust, B; Shintre, CA; Carpenter, EP; Srinivasan, V; van Veen, HW; Balk, J;
Biochemical Society Transactions. 2015 43:943-951. doi: 10.1042/bst20150118
PMID: 26517908

K2P channel gating mechanisms revealed by structures of TREK-2 and a complex with Prozac.
Dong, YY; Pike, ACW; Mackenzie, A; McClenaghan, C; Aryal, P; Dong, L; Quigley, A; Grieben, M; Goubin, S; Mukhopadhyay, S; Ruda, GF; Clausen, MV; Cao, L; Brennan, PE; Burgess-Brown, NA; Sansom, MSP; Tucker, SJ; Carpenter, EP;
Science. 2015 347:1256-1259. doi: 10.1126/science.1261512
PMID: 25766236

MemProtMD: Automated Insertion of Membrane Protein Structures into Explicit Lipid Membranes.
Stansfeld, PJ; Goose, JE; Caffrey, M; Carpenter, EP; Parker, JL; Newstead, S; Sansom, MS;
Structure. 2015 23:1350-1361. doi: 10.1016/j.str.2015.05.006
PMID: 26073602

ATP Binding and Hydrolysis Properties of ABCB10 and Their Regulation by Glutathione.
Qiu, W; Liesa, M; Carpenter, EP; Shirihai, OS;
PLoS ONE. 2015 10:e0129772-. doi: 10.1371/journal.pone.0129772
PMID: 26053025

2014

Purification and interaction analyses of two human lysosomal vitamin B12 transporters: LMBD1 and ABCD4.
Deme, JC; Hancock, MA; Xia, X; Shintre, CA; Plesa, M; Kim, JC; Carpenter, EP; Rosenblatt, DS; Coulton, JW;
Molecular Membrane Biology. 2014 31:250-261. doi: 10.3109/09687688.2014.990998
PMID: 25535791

2013

The structural basis of ZMPSTE24-dependent laminopathies
Quigley, A; Dong, YY; Pike, ACW; Dong, L; Shrestha, L; Berridge, G; Stansfeld, PJ; Sansom, MSP; Edwards, AM; Bountra, C; Von Delft, F; Bullock, AN; Burgess-Brown, NA; Carpenter, EP;
Science. 2013 340:1604-1607. doi: 10.1126/science.1231513
PMID:

2012

Structural basis for the recognition and cleavage of abasic DNA in Neisseria meningitidis.
Lu, D; Silhan, J; MacDonald, JT; Carpenter, EP; Jensen, K; Tang, CM; Baldwin, GS; Freemont, PS;
Proceedings of the National Academy of Sciences. 2012 109:16852-16857. doi: 10.1073/pnas.1206563109
PMID: 23035246

An analysis of subdomain orientation, conformational change and disorder in relation to crystal packing of aspartic proteinases.
Bailey, D; Carpenter, EP; Coker, A; Coker, S; Read, J; Jones, AT; Erskine, P; Aguilar, CF; Badasso, M; Toldo, L; Rippmann, F; Sanz-Aparicio, J; Albert, A; Blundell, TL; Roberts, NB; Wood, SP; Cooper, JB;
Acta Crystallographica Section D: Biological Crystallography. 2012 68:541-552. doi: 10.1107/S0907444912004817
PMID: 22525752

2011

Crystal structure of a prokaryotic homologue of the mammalian oligopeptide-proton symporters, PepT1 and PepT2.
Newstead, S; Drew, D; Cameron, AD; Postis, VLG; Xia, X; Fowler, PW; Ingram, JC; Carpenter, EP; Sansom, MSP; McPherson, MJ; Baldwin, SA; Iwata, S;
EMBO Journal. 2011 30:417-426. doi: 10.1038/emboj.2010.309
PMID: 21131908

High-performance liquid chromatography separation and intact mass analysis of detergent-solubilized integral membrane proteins.
Berridge, G; Chalk, R; D'Avanzo, N; Dong, L; Doyle, D; Kim, J-I; Xia, X; Burgess-Brown, N; Deriso, A; Carpenter, EP; Gileadi, O;
Analytical Biochemistry. 2011 410:272-280. doi: 10.1016/j.ab.2010.11.008
PMID: 21093405

2010

Four distinct structural domains in Clostridium difficile toxin B visualized using SAXS.
Albesa-Jové, D; Bertrand, T; Carpenter, EP; Swain, GV; Lim, J; Zhang, J; Haire, LF; Vasisht, N; Braun, V; Lange, A; von Eichel-Streiber, C; Svergun, DI; Fairweather, NF; Brown, KA;
Journal of Molecular Biology. 2010 396:1260-1270. doi: 10.1016/j.jmb.2010.01.012
PMID: 20070948

2009

Insights into how nucleotide-binding domains power ABC transport.
Newstead, S; Fowler, PW; Bilton, P; Carpenter, EP; Sadler, PJ; Campopiano, DJ; Sansom, MSP; Iwata, S;
Structure. 2009 17:1213-1222. doi: 10.1016/j.str.2009.07.009
PMID: 19748342

Crystal structure of the acid-induced arginine decarboxylase from Escherichia coli: reversible decamer assembly controls enzyme activity.
Andréll, J; Hicks, MG; Palmer, T; Carpenter, EP; Iwata, S; Maher, MJ;
Biochemistry. 2009 48:3915-3927. doi: 10.1021/bi900075d
PMID: 19298070

2008

Insights into outer membrane protein crystallization.
Newstead, S; Hobbs, J; Jordan, D; Carpenter, EP; Iwata, S;
Molecular Membrane Biology. 2008 25:631-638. doi: 10.1080/09687680802526574
PMID: 19023694

Structure and molecular mechanism of a nucleobase-cation-symport-1 family transporter.
Weyand, S; Shimamura, T; Yajima, S; Suzuki, S; Mirza, O; Krusong, K; Carpenter, EP; Rutherford, NG; Hadden, JM; O'Reilly, J; Ma, P; Saidijam, M; Patching, SG; Hope, RJ; Norbertczak, HT; Roach, PCJ; Iwata, S; Henderson, PJF; Cameron, AD;
Science. 2008 322:709-713. doi: 10.1126/science.1164440
PMID: 18927357

Overcoming the challenges of membrane protein crystallography.
Carpenter, EP; Beis, K; Cameron, AD; Iwata, S;
Current Opinion in Structural Biology. 2008 18:581-586. doi: 10.1016/j.sbi.2008.07.001
PMID: 18674618

Thioredoxin A active-site mutants form mixed disulfide dimers that resemble enzyme-substrate reaction intermediates.
Kouwen, TRHM; Andréll, J; Schrijver, R; Dubois, J-YF; Maher, MJ; Iwata, S; Carpenter, EP; van Dijl, JM;
Journal of Molecular Biology. 2008 379:520-534. doi: 10.1016/j.jmb.2008.03.077
PMID: 18455736

2007

Atomic resolution insight into host cell recognition by Toxoplasma gondii.
Blumenschein, TMA; Friedrich, N; Childs, RA; Saouros, S; Carpenter, EP; Campanero-Rhodes, MA; Simpson, P; Chai, W; Koutroukides, T; Blackman, MJ; Feizi, T; Soldati-Favre, D; Matthews, S;
EMBO Journal. 2007 26:2808-2820. doi: 10.1038/sj.emboj.7601704
PMID: 17491595

AP endonuclease paralogues with distinct activities in DNA repair and bacterial pathogenesis.
Carpenter, EP; Corbett, A; Thomson, H; Adacha, J; Jensen, K; Bergeron, J; Kasampalidis, I; Exley, R; Winterbotham, M; Tang, C; Baldwin, GS; Freemont, P;
EMBO Journal. 2007 26:1363-1372. doi: 10.1038/sj.emboj.7601593
PMID: 17318183

High-level bacterial expression and purification of apicomplexan micronemal proteins for structural studies.
Saouros, S; Blumenschein, TMA; Sawmynaden, K; Marchant, J; Koutroukides, T; Liu, B; Simpson, P; Carpenter, EP; Matthews, SJ;
Protein and Peptide Letters. 2007 14:411-415. doi:
PMID: 17584164

The cell-binding region of Toxoplasma gondii micronemal protein 1 presents a novel fold
Blumenschein, TMA; Carpenter, EP; Saciuros, S; Friedrich, N; Koutroukides, T; Soldati, D; Matthews, S;
Biophysical Journal. 2007 :43A-43A. doi:
PMID:

2006

A comparative study of uracil-DNA glycosylases from human and herpes simplex virus type 1.
Krusong, K; Carpenter, EP; Bellamy, SRW; Savva, R; Baldwin, GS;
Journal of Biological Chemistry. 2006 281:4983-4992. doi: 10.1074/jbc.M509137200
PMID: 16306042

2005

Structure of a central stalk subunit F of prokaryotic V-type ATPase/synthase from Thermus thermophilus.
Makyio, H; Iino, R; Ikeda, C; Imamura, H; Tamakoshi, M; Iwata, M; Stock, D; Bernal, RA; Carpenter, EP; Yoshida, M; Yokoyama, K; Iwata, S;
EMBO Journal. 2005 24:3974-3983. doi: 10.1038/sj.emboj.7600859
PMID: 16281059

2003

Twists and turns: a tale of two shikimate-pathway enzymes.
Brown, KA; Carpenter, EP; Watson, KA; Coggins, JR; Hawkins, AR; Koch, MHJ; Svergun, DI;
Biochemical Society Transactions. 2003 31:543-547. doi:
PMID: 12773153

Protein farnesyl and N-myristoyl transferases: piggy-back medicinal chemistry targets for the development of antitrypanosomatid and antimalarial therapeutics.
Gelb, MH; Van Voorhis, WC; Buckner, FS; Yokoyama, K; Eastman, R; Carpenter, EP; Panethymitaki, C; Brown, KA; Smith, DF;
Molecular and Biochemical Parasitology. 2003 126:155-163. doi:
PMID: 12615314

2000

Multistep catalysis dehydroquinate synthase.
Brown, KA; Carpenter, EP;
FASEB Journal. 2000 14:A1583-A1583. doi:
PMID:

1999

PCR-based gene synthesis as an efficient approach for expression of the A+T-rich malaria genome.
Withers-Martinez, C; Carpenter, EP; Hackett, F; Ely, B; Sajid, M; Grainger, M; Blackman, MJ;
Protein Engineering, Design and Selection. 1999 12:1113-1120. doi:
PMID: 10611405

1998

Structure of dehydroquinate synthase reveals an active site capable of multistep catalysis.
Carpenter, EP; Hawkins, AR; Frost, JW; Brown, KA;
Nature. 1998 394:299-302. doi: 10.1038/28431
PMID: 9685163

1111

High-performance liquid chromatography separation and intact mass analysis of detergent-solubilized integral membrane proteins
Berridge, G; Chalk, R; Burgess-Brown, NA; Carpenter, EP; Gileadi, O;
Analytical Biochemistry. 1111 :-. doi: 10.1016/j.ab.2010.11.008
PMID:

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