Other Targets Drug Discovery Assays and Products

Membrane proteins are key targets for the pharmaceutical industry because of their numerous and significant functional activities. Transmembrane proteins make up approximately 20–30% of the proteomes of most animals, or about 5500 proteins in humans. Prior topology-based investigations of membrane proteins in the human genome have demonstrated that the largest group of α-helical membrane proteins has only one transmembrane spanning helix, whereas the second largest category contains the proteins with two transmembrane helixes.

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• Membrane Protein in Vitro Assay Kits
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• Membranes
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4TM Membrane Proteins

The four-transmembrane helix-containing proteins are distinguished by a variety of protein families, including the neurotransmitter-gated ion channels, claudins, connexins, and tetraspanins, that exhibit high degrees of functional diversity. These TM families are categorized by the number of -helices that span the membrane. Another significant 4TM family is the claudins, which are one of the key structural elements of tight junctions and regulate cell-cell adhesion. Since connexins are the structural elements of gap junctions, which are crucial in cell-cell communication, and are also members of the Transporter superfamily, they have received a great deal of research attention. Finally, there are 33 members of the tetraspanin family, some of which are widely and abundantly expressed throughout tissues while others are expressed more selectively. These tetraspanins have a conserved CCG motif with 4-6 conserved extracellular cysteine residues and the tetraspanin functional domain, which belongs to the Tetraspanin-like clan.

Fig.1 Common topologies and conserved features within the 4TM membrane proteins. (Attwood, et al., 2016)

1TM Membrane Proteins

Except for immunoglobulins, 58% of the 1,113 non-human proteins belonging to any family found in the Structure/Adhesion class are expected to have only one TM, whereas 20% are anticipated to have a topology with four TMs. This shows that humans and other species both have a similar relative frequency of the 1 TM and 4 TM Structure/Adhesion proteins. The 'Other' and 'Protein of uncertain function' groups, which make up 25% and 16% of each group, also contain proteins with a 4 TM structure.

Fig.2 Transmembrane topology analysis. (Almén, et al., 2009)

β-Barrel Proteins

The barrel-like structure of barrel proteins is made up of β-sheets. The residues are often alternately hydrophobic and polar in this sequence pattern because the residues in each sheet alternately point outward, toward the lipids, and inward, toward the interior of the barrel. The end result is a polar conduit that water-soluble molecules can pass through. Around 2-3% of the genes in gram-negative bacteria are thought to encode β-barrel membrane proteins. A small number of β-barrel proteins are also present in the chloroplast and mitochondrial outer membranes.

References

1. Attwood, M.M.; et al. Topology based identification and comprehensive classification of four-transmembrane helix containing proteins (4TMs) in the human genome. BMC genomics. 2016, 17(1): 1-16.
2. Almén, M.S.; et al. Mapping the human membrane proteome: a majority of the human membrane proteins can be classified according to function and evolutionary origin. BMC biology. 2009, 7(1): 1-14.