MPL Photo Gallery

This Structure Gallery shows some examples of membrane protein structures successfully solved by MPL researchers and MPL users/collaborators.

ACRB

The structure of the efflux pump AcrB in complex with bile acid

Gastrointestinal bacteria, like Escherichia coli, must remove bile acid to survive in the gut. Bile acid removal in E. coli is thought to be mediated primarily by the multidrug efflux pump, AcrB. All evidence suggests that bile acid is transported out of the cell via the periplasmic vestibule of the AcrAB-TolC complex.

Reference:

D.Drew, M.M.Klepsch, S.Newstead, R.Flaig, J.W.De Gier, S.Iwata, K.Beis.”The structure of the efflux pump AcrB in complex with bile acid”.Mol Membr Biol 25:677-682 (2008).

PDB code: 2W1B

Crystal structure of a nucleobase-cation-symport-1 family transporter (MHP1)

The nucleobase-cation-symport-1 (NCS1) benzyl-hydantoin transporter (Mhp1) is an essential component of salvage pathways for nucleobases and related metabolites. The structures of the outward-facing open and substrate-bound occluded conformations were solved, showing how the outward-facing cavity closes upon binding of substrate.

Reference:

Shimamura, T., Weyand, S., Beckstein, O., Rutherford, N.G., Hadden, J.M., David Sharples, D., Sansom, M.S.P., Iwata, S., Henderson P.J.F. & Cameron, A.D. “Molecular Basis of Alternating Access Membrane Transport by the Sodium- Hydantoin Transporter, Mhp1”. Science. 328: 470-473 (2010).

Weyand, S., Shimamura, T., Yajima, S., Suzuki, S., Mirza O., Krusong, K., Carpenter, E.P., Rutherford, N.G., Hadden, J.M., OReilly, J., Ma, P., Saidijam, M., Patching, S.G., Hope, R.J., Norbertczak, H.T., Roach, P.C.J., Iwata, S., Henderson, P.J. F. and Cameron, A.D. “Molecular basis of the alternating access model of membrane transport: structure of a nucleobase-cation-symport-1 family transporter”. Science 322: 709-713 (2008).

PDB codes: 2JLN, 2JLO and 2X79

Crystal Structure of a Proton Dependent Oligopeptide (POT) Family Transporter

The crystal structure of PepT(So) form the Shewanella oneidensis represents a sound model system for understanding mammalian peptide transport as catalysed by PepT1 and PepT2. PepT1 and PepT2 are major facilitator superfamily (MFS) transporters that utilize a proton gradient to drive the uptake of di- and tri-peptides in the small intestine and kidney, respectively.

Reference:

Newstead, S., Drew, D., Cameron, A.D., Postis, V.L., Xia, X., Fowler, P.W., Ingram, J.C., Carpenter, E.P., Sansom, M.S., McPherson, M.J., Baldwin, S.A., Iwata, S. “Crystal structure of a prokaryotic homologue of the mammalian oligopeptide-proton symporters, PepT1 and PepT2”. EMBO J 30: 417 - 426 (2010).

PDB code: 2XUT

H1

Crystal Structure of the human Histamine Receptor

The biogenic amine histamine is an important pharmacological mediator involved in pathophysiological processes such as allergies and inflammations. Histamine H1 receptor (H(1)R) antagonists are very effective drugs alleviating the symptoms of allergic reactions.

Reference:

Shimamura T, Shiroishi M, Weyand S, Tsujimoto H, Winter G, Katritch V, Abagyan R, Cherezov V, Liu W, Han GW, Kobayashi T, Stevens RC, Iwata S. “Structure of the human histamine H1 receptor complex with doxepin”. Nature 475:65-82 (2011).

PDB code: 3RZE

isabel2

Crystal structure of a bacterial homologue of the bile acid sodium sodium symporter ASBT

The structure of bacterial homologue of the Apical Sodium dependent Bile Acid Transporter (ASBT) is a target for hypercholesterolemia drugs since it can affect the level of cholesterol in the blood. It is known that by blocking ASBT, bile acid levels returning to the liver are lowered, the liver therefore converts more cholesterol into bile acids, which lowers the level of cholesterol in the blood.

Reference:

Hu NJ, Iwata S, Cameron AD, Drew D. “Crystal structure of a bacterial homologue of the bile acid sodium symporter ASBT”. Nature 478:408-11 (2011).

PDB code: 3ZUY and 3ZUX

Vasan

The structure of monoacylglycerol lipase from Bacillus sp. H257

Monoacylglycerol lipases (MGLs) catalyse the hydrolysis of monoacylglycerol into free fatty acid and glycerol. MGLs have been identified throughout all genera of life and have adopted different substrate specificities depending on their physiological role. In humans, MGL plays an integral part in lipid metabolism affecting energy homeostasis, signalling processes and cancer cell progression. In bacteria, MGLs degrade short-chain monoacylglycerols which are otherwise toxic to the organism.

Reference:

Rengachari, Srinivasan, Gustavo A. Bezerra, Lina Riegler-Berket, Christian C. Gruber, Christian Sturm, Ulrike Taschler, Andras Boeszoermenyi et al. "The structure of monoacylglycerol lipase from Bacillus sp. H257 reveals unexpected conservation of the cap architecture between bacterial and human enzymes." Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids 1821:1012-1021 (2012).

PDB code: 3RM3 and 3RLI

bW

Structure of a bacterial voltage-gated sodium channel

Voltage-gated sodium channels are vital membrane proteins essential for electrical signaling. In humans, they are key targets for the development of pharmaceutical drugs. The crystal structure of the open-channel conformation of NavMs, the bacterial channel pore from the marine bacterium Magnetococcus sp. (strain MC-1) have revealed mechanisms of opening and closing.

Reference:

McCusker, E. C., Bagnéris, C., Naylor, C. E., Cole, A. R., D'Avanzo, N., Nichols, C. G., & Wallace, B. A. “Structure of a bacterial voltage-gated sodium channel pore reveals mechanisms of opening and closing”. Nat Communications 3: 1102 (2012).

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ACRB

The structure of the efflux pump AcrB in complex with bile acid

Reference:

PDB code: 2W1B

Crystal structure of a nucleobase-cation-symport-1 family transporter (MHP1)

Reference:

PDB codes: 2JLN, 2JLO and 2X79

Crystal Structure of a Proton Dependent Oligopeptide (POT) Family Transporter

Reference:

PDB code: 2XUT

H1

Crystal Structure of the human Histamine Receptor

Reference:

PDB code: 3RZE

isabel2

Crystal structure of a bacterial homologue of the bile acid sodium sodium symporter ASBT

Reference:

PDB code: 3ZUY and 3ZUX

Vasan

The structure of monoacylglycerol lipase from Bacillus sp. H257

Reference:

PDB code: 3RM3 and 3RLI

bW

Structure of a bacterial voltage-gated sodium channel

Reference:

PDB code: 3RZE