Transporter transmembrane segments

Figure 41-17. Diagram of the structure of the CFTR protein (not to scale). The protein contains twelve transmembrane segments (probably helical), two nucleotide-binding folds or domains (NBFl and NBF2), and one regulatory (R) domain. NBFl and NBF2 probably bind ATP and couple its hydrolysis to transport of Cl . Phe 508, the major locus of mutations in cystic fibrosis, is located in NBFl.

Figure 8.6 Schematic diagram of the proposed structure of the vesicular monoamine transporter. There are 12 transmembrane segments with both the N- and C-termini projecting towards the neuronal cytosol. (Based on Schuldiner 1998)...

Hydropathy plots [133] of the slow and fast Ca -ATPase isoenzymes are nearly identical and provide unambiguous prediction of four of the proposed transmembrane segments (Mi, M2, M3 and M4) [8,11]. Similar hydropathy plots were also obtained for other closely related cation transporting ATPases [31,46,47,134]. 

Ion channels, transporters and many receptors are polytopic. Polar and helix-destabilizing residues are likely to occur within their transmembrane segments to form the requisite gates, channels or binding domains. Transmembrane helices in polytopic proteins are usually... 

SLC2 (solute carrier) superfamily consists of 12 glucose transporters (GLUT1-12) and one H+-myo-inositol cotransporter (HMIT or GLUT13). They all have 12 transmembrane segments with the N- and C-termini both on the cytoplasmic aspect and a specific N-linked oligosaccharide side-chain on either the first or fourth extracellular loop. 

The neuronal membrane norepinephrine transporter (NET), the dopamine transporter (DAT) and the vesicular membrane transporter (VMAT-2), which is the same in all catecholamine-containing neurons, have similar numbers of predicted transmembrane segments. They have different numbers of amino acids, pharmacological properties and chromosomal localizations. 

Hastrup, H., Karlin, A., and Javitch, J. A. (2001) Symmetrical dimer of the human dopamine transporter revealed by cross-linking Cys-306 at the extracellular end of the sixth transmembrane segment. Proc. Natl. Acad. Sci. USA 98,10055-10060. 

We have developed a common residue numbering scheme that facilitates comparison of the sequences of different NTs. The numbering scheme is informative of the relative position of each amino acid, the amino acid present at that position, and the actual amino acid number in a particular transporter. Each index number starts with the number of the transmembrane segment (TM), e.g., 1 for TM1, and is followed by a number indicating the position relative to a reference residue that is the most conserved position in that TM. That reference residue is arbitrarily assigned the number 50. For exam-... 

Figure 6.1. Topological model for the HoxN nickel permease of R. eutropha that is like the HupN of B. japonicum (Eitinger et al. 1997). The residues (two histidines and one aspartic acid) in the second transmembrane segment were shown to be key residues for nickel transport, and this motif (His-Xaa4-Asp-His) is conserved in nickel-transport proteins. Bold, residues studied by site-directed mutagenesis.

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