Uma equipe de cientistas liderada pelo professor da Universidade Rosalind Franklin, David M. Mueller, resolveu a estrutura da ATP sintase mitocondrial, uma enzima que produz o ATP,ligada a membrana lipídica!

High-resolution cryo-EM analysis of the yeast ATP synthase in a lipid membrane

Anurag P. Srivastava,1 * Min Luo,2* Wenchang Zhou,3 Jindrich Symersky,1 Dongyang Bai,1 Melissa G. Chambers,2 José D. Faraldo-Gómez,3 Maofu Liao,2† David M. Mueller1 † 

1 Department of Biological Chemistry and Molecular Biology, Chicago Medical School, Rosalind Franklin University, 3333 Green Bay Road, North Chicago, IL 60064, USA. 2 Department of Cell Biology, Harvard Medical School, 250 Longwood Avenue, SGM 509, Boston, MA 02115, USA. 3 Theoretical Molecular Biophysics Laboratory, National Heart, Lung, and Blood Institute, National Institutes of Health, 50 South Drive, Bethesda, MD 20892, USA. *These authors contributed equally to this work. 

†Corresponding author. Email: david.mueller@rosalindfranklin.edu (D.M.M.); maofu_liao@hms.harvard.edu (M.L.)

Abstract:

Mitochondrial ATP synthase comprises a membrane embedded Fo motor that rotates to drive ATP synthesis in the F1 subunit. We used single-particle cryo-EM to obtain structures of the full complex in a lipid bilayer in the absence or presence of the inhibitor oligomycin, at 3.6 Å and 3.8 Å resolution, respectively. To limit conformational heterogeneity, we locked the rotor in a single conformation by fusing the F6 subunit of the stator with the δ-subunit of the rotor. Assembly of the enzyme with the F6-δ fusion caused a twisting of the rotor and a 9° rotation of the Fo c10-ring in the direction of ATP synthesis, relative to the structure of isolated Fo. Our cryo-EM structures show how F1 and Fo are coupled, give insight into the proton translocation pathway and show how oligomycin blocks ATP synthesis.

Full text: http://science.sciencemag.org/content/early/2018/04/11/science.aas9699

Enviado por: Professor Francisco Pereira Júnior da UFCA

Postado por: Hadson Bastos