The Membrane Topography of the Diphtheria Toxin T Domain Linked to the A Chain Reveals a Transient Transmembrane Hairpin and Potential Translocation Mechanisms Export

@article{citeulike:5913396, abstract = {The diphtheria toxin T domain helps translocate the A chain of the toxin across membranes. To gain insight into translocation, the membrane topography of key residues in T domain attached to the A chain (AT protein) was compared to that in the isolated T domain using fluorescence techniques. This study demonstrates that residues in T domain hydrophobic helices (TH5−TH9) tended to be less exposed to aqueous solution in the AT protein than in the isolated T domain. Under conditions in which the loop connecting TH5 to TH6/7 is located stably on the cis (insertion) side of the membrane in the isolated T domain, it moves between the cis and trans sides of the membrane in the AT protein. This is indicative of the formation of a dynamic, transient transmembrane hairpin topography by TH5−TH7 in the AT protein. Since TH8 and TH9 also form a transmembrane hairpin, this means that TH5−TH9 may form a cluster of transmembrane helices. These helices have a nonpolar surface likely to face the lipid bilayer in a helix cluster and a surface rich in uncharged hydrophilic residues which in a helix cluster would likely be facing inward (and perhaps be pore-lining). This uncharged hydrophilic surface could play a crucial role in translocation, interacting transiently with the translocating A chain. A similar motif can be found in, and may be important for, other protein translocation systems.}, author = {Wang, Jie and London, Erwin}, citeulike-article-id = {5913396}, citeulike-linkout-0 = {http://dx.doi.org/10.1021/bi9014665}, citeulike-linkout-1 = {http://pubs.acs.org/doi/abs/10.1021/bi9014665}, doi = {10.1021/bi9014665}, journal = {Biochemistry}, keywords = {diptheria, mechanism, membrane, topology, toxin, transien, translocation, transmembrane, wang09pdf}, number = {0}, posted-at = {2009-10-09 00:30:59}, priority = {2}, title = {The Membrane Topography of the Diphtheria Toxin T Domain Linked to the A Chain Reveals a Transient Transmembrane Hairpin and Potential Translocation Mechanisms}, url = {http://dx.doi.org/10.1021/bi9014665}, volume = {0}, year = {0000} }

TY - JOUR ID - citeulike:5913396 L3 - citeulike-article-id:5913396 N2 - The diphtheria toxin T domain helps translocate the A chain of the toxin across membranes. To gain insight into translocation, the membrane topography of key residues in T domain attached to the A chain (AT protein) was compared to that in the isolated T domain using fluorescence techniques. This study demonstrates that residues in T domain hydrophobic helices (TH5−TH9) tended to be less exposed to aqueous solution in the AT protein than in the isolated T domain. Under conditions in which the loop connecting TH5 to TH6/7 is located stably on the cis (insertion) side of the membrane in the isolated T domain, it moves between the cis and trans sides of the membrane in the AT protein. This is indicative of the formation of a dynamic, transient transmembrane hairpin topography by TH5−TH7 in the AT protein. Since TH8 and TH9 also form a transmembrane hairpin, this means that TH5−TH9 may form a cluster of transmembrane helices. These helices have a nonpolar surface likely to face the lipid bilayer in a helix cluster and a surface rich in uncharged hydrophilic residues which in a helix cluster would likely be facing inward (and perhaps be pore-lining). This uncharged hydrophilic surface could play a crucial role in translocation, interacting transiently with the translocating A chain. A similar motif can be found in, and may be important for, other protein translocation systems. IS - 0 JF - Biochemistry TI - The Membrane Topography of the Diphtheria Toxin T Domain Linked to the A Chain Reveals a Transient Transmembrane Hairpin and Potential Translocation Mechanisms VL - 0 KW - diptheria KW - mechanism KW - membrane KW - topology KW - toxin KW - transien KW - translocation KW - transmembrane KW - wang09pdf AU - Wang, Jie AU - London, Erwin PY - 2000/// UR - http://dx.doi.org/10.1021/bi9014665 ER -