Antagonistic effect of ganglioside GM1 and GM3 on the activity and conformation of sarcoplasmic reticulum Ca(2+)-ATPase.
It was found that rabbit skeletal muscle sarcoplasmic reticulum (SR) contained two main gangliosides: NeuNAc alpha 2-->3 Gal beta 1-->4 Glc beta 1-->1'ceramide (GM3) and Gal beta 1-->3 GalNAc beta 1-->4(NeuNAc alpha 2-->3) Gal beta 1-->4 Glc beta 1-->1'ceramide (GM1), and that the most abundant ganglioside GM3 could positively modulate the SR Ca(2+)-ATPase activity. In this paper, the effect of GM1 on Ca(2+)-ATPase was further investigated and compared with that of GM3. The study demonstrates that GM1 has an opposite effect with respect to GM3 on the activity of SR Ca(2+)-ATPase. Using assays, including intrinsic and time-resolved fluorescence and fluorescence quenching, the conformational changes of SR Ca(2+)-ATPase induced by GM1 and GM3 were compared. Obtained results indicate that GM1 could make the Ca(2+)-ATPase molecules less compact in the hydrophilic domain but more compact in the hydrophobic domain, while GM3 makes the enzyme more compact in both the hydrophilic and hydrophobic domain. Homogeneous GM1 and GM3 with the same ceramide moiety had similar effects on SR Ca(2+)-ATPase activities compared to their natural counterparts, suggesting that the carbohydrate chain may be the key moiety of the ganglioside molecule to be responsible for the difference of the effect on enzyme activity.
Wang
Y
Y
Department of Biochemistry, Dalian Medical University, China.
Tsui
Z
Z
Yang
F
F
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism*; D002417:Cattle; D002518:Ceramides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005677:G(M1) Ganglioside / Q000378:metabolism* / Q000502:physiology; D005679:G(M3) Ganglioside / Q000378:metabolism* / Q000502:physiology; D066298:In Vitro Techniques; D007700:Kinetics; D010569:Perylene / Q000031:analogs & derivatives / Q000494:pharmacology; D017319:Photosensitizing Agents / Q000494:pharmacology; D011193:Potassium Iodide / Q000494:pharmacology; D011809:Quinones / Q000494:pharmacology; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000201:enzymology*; D013050:Spectrometry, Fluorescence; D014364:Tryptophan / Q000378:metabolism
D002518:Ceramides; D005679:G(M3) Ganglioside; D017319:Photosensitizing Agents; D011809:Quinones; D011193:Potassium Iodide; D005677:G(M1) Ganglioside; D010569:Perylene; D014364:Tryptophan; D000255:Adenosine Triphosphate; D000252:Calcium-Transporting ATPases; D002118:Calcium; C064522:hypocrellin B