High impact information on TSPAN16

• Both mutants carry single point mutations leading to non-conservative amino acid substitutions that affect two putative transmembrane (TM) domains (tlt, Ala(151)-->Glu in TM3; mlh, Leu(408)-->Gln in TM8) [1].
• Structure-function studies of mammalian and bacterial excitatory amino acid transporters (EAATs), as well as the crystal structure of a related archaeal glutamate transporter, support a model in which TM7, TM8, and the re-entrant loops HP1 and HP2 participate in forming a substrate translocation pathway within each subunit of a trimer [2].
• Previously we obtained evidence based on engineering of Zn2+ binding sites that the extracellular parts of transmembrane segment 7 (TM7) and TM8 in the human dopamine transporter are important for transporter function [3].
• To further evaluate the role of this domain, we have employed the substituted cysteine accessibility method and performed 10 single cysteine substitutions at the extracellular ends of TM7 and TM8 [3].
• Ala-854 has been mutated to Glu, Asp, or Gln; Glu-975 in TM8, which is an Ala in the SERCA pump, has been mutated to Gln, Asp, or Ala [4].

Biological context of TSPAN16

• TM4-B was mapped to the q34 region on human chromosome 9 [5].
• By contrast, biotinylation of cysteine residues located in the predicted cytoplasmic loops between TM2 and TM3, TM4 and TM5, TM8 and TM9, or TM10 and TM11 were not blocked by pretreatment with membrane impermeant maleimide, suggesting that these residues were in the cytoplasm [6].
• We conclude that MSD2-charged residues in or proximal to TM6, TM7, TM8, and TM11 play critical but differential roles in MRP1 transport activity and substrate specificity [7].
• Strain TM-8 was identified as Methanobacterium formicicum based on its physiology and phylogeny [8].

Anatomical context of TSPAN16

• Two of the three TM8 mutants were correctly delivered to the plasma membrane and were active [4].

Associations of TSPAN16 with chemical compounds

• The close association between TM 7 and 8 was further established by engineering of a Zn(2+)-binding site between His(375) and a cysteine inserted in position 400 in TM 8 [9].
• Mutation of Glu(396) (E396Q) at the top of TM 8 increased the IC(50) value for Zn(2+) inhibition of [(3)H]dopamine uptake from 1.1 to 530 microM and eliminated Zn(2+)-induced potentiation of [(3)H]WIN 35,428 binding [9].
• The additional mutation of Ser(353) to Thr in TM 8 converted hCNT1/S319G/Q320M, from cib to cif, but with relatively low adenosine transport activity [10].
• The CD spectra of the polyheptapeptides TM-8, TM-15, and TM-22 show large increases in molar ellipticity at 220 nm on the addition of trifluoroethanol (helix-inducing solvent) to the benign buffer [11].
• The peptides TM-8, TM-15, and TM-22 were shown to be monomeric in both denaturant (8 M urea) and benign medium by gel-filtration high-performance liquid chromatography on TSK G2000 SW while peptides TM-29 and TM-36 were shown to be dimeric in benign medium both by gel-filtration and sedimentation equilibrium experiments [11].

Other interactions of TSPAN16

• TM4-B is a novel member of the Tetraspanin superfamily and displays characteristics typical of the superfamily [5].

Analytical, diagnostic and therapeutic context of TSPAN16

• The results of these binding studies are in good agreement with current site-directed mutagenesis data and support the suggestion that the binding site is proximal to the loop between TM5 and TM6 and TM8, the transmembrane (TM) region considered important for cation translocation [12].
• A syntrophic butyrate-degrading bacterium, strain TB-6, was isolated in coculture with strain TM-8 from paddy soil [8].

References