Lanthanum ions inhibit the mammalian Sec61 complex in its channel dynamics and protein transport activity.
Previous electrophysiological experiments characterized the Sec61 complex, which provides the aqueous path for entry of newly-synthesized polypeptides into the mammalian endoplasmic reticulum, as a highly dynamic channel that, once activated by precursor proteins, fluctuates between main open states with mean conductances of 220 and 550pS. Millimolar concentrations of lanthanum ions simultaneously restricted the dynamics of the Sec61 channel and inhibited translocation of polypeptides. Molecular modeling indicates that lanthanum binding sites cluster at the putative lateral gate of the Sec61 complex and suggests that structural flexibility of the lateral gate is essential for channel and protein transport activities of the Sec61 complex.
Erdmann
Frank
F
Biophysik, Universität Osnabrück, FB Biologie/Chemie, D-49034 Osnabrück, Germany.
Jung
Martin
M
Eyrisch
Susanne
S
Lang
Sven
S
Helms
Volkhard
V
Wagner
Richard
R
Zimmermann
Richard
R
D000818:Animals; D001665:Binding Sites; D004285:Dogs; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D007477:Ions / Q000378:metabolism*; D007811:Lanthanum / Q000378:metabolism*; D046911:Macromolecular Substances / Q000737:chemistry / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation; D021381:Protein Transport / Q000502:physiology*; D000069816:SEC Translocation Channels
D007477:Ions; D046911:Macromolecular Substances; D008565:Membrane Proteins; D000069816:SEC Translocation Channels; D007811:Lanthanum