Structure of the C(10) Ring of the Yeast Mitochondrial ATP Synthase in the Open Conformation

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2012 Apr 17

PMID 22504883

Citations 65

Authors

Jindrich Symersky

Vijayakanth Pagadala

Daniel Osowski

Alexander Krah

Thomas Meier

Jose D Faraldo-Gomez

David M Mueller

Affiliations

Soon will be listed here.

Abstract

The proton pore of the F(1)F(o) ATP synthase consists of a ring of c subunits, which rotates, driven by downhill proton diffusion across the membrane. An essential carboxylate side chain in each subunit provides a proton-binding site. In all the structures of c-rings reported to date, these sites are in a closed, ion-locked state. Structures are here presented of the c(10) ring from Saccharomyces cerevisiae determined at pH 8.3, 6.1 and 5.5, at resolutions of 2.0 Å, 2.5 Å and 2.0 Å, respectively. The overall structure of this mitochondrial c-ring is similar to known homologs, except that the essential carboxylate, Glu59, adopts an open extended conformation. Molecular dynamics simulations reveal that opening of the essential carboxylate is a consequence of the amphiphilic nature of the crystallization buffer. We propose that this new structure represents the functionally open form of the c subunit, which facilitates proton loading and release.

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References

Staritzbichler R, Anselmi C, Forrest L, Faraldo-Gomez J . GRIFFIN: A versatile methodology for optimization of protein-lipid interfaces for membrane protein simulations. J Chem Theory Comput. 2014; 7(4):1167-1176. PMC: 3972769. DOI: 10.1021/ct100576m. View

Mizutani K, Yamamoto M, Suzuki K, Yamato I, Kakinuma Y, Shirouzu M . Structure of the rotor ring modified with N,N'-dicyclohexylcarbodiimide of the Na+-transporting vacuolar ATPase. Proc Natl Acad Sci U S A. 2011; 108(33):13474-9. PMC: 3158168. DOI: 10.1073/pnas.1103287108. View

Preiss L, Yildiz O, Hicks D, Krulwich T, Meier T . A new type of proton coordination in an F(1)F(o)-ATP synthase rotor ring. PLoS Biol. 2010; 8(8):e1000443. PMC: 2914638. DOI: 10.1371/journal.pbio.1000443. View

Abrahams J, Leslie A, Lutter R, Walker J . Structure at 2.8 A resolution of F1-ATPase from bovine heart mitochondria. Nature. 1994; 370(6491):621-8. DOI: 10.1038/370621a0. View

Baker N, Sept D, Joseph S, Holst M, McCammon J . Electrostatics of nanosystems: application to microtubules and the ribosome. Proc Natl Acad Sci U S A. 2001; 98(18):10037-41. PMC: 56910. DOI: 10.1073/pnas.181342398. View

Ujwal R, Bowie J . Crystallizing membrane proteins using lipidic bicelles. Methods. 2011; 55(4):337-41. PMC: 3264687. DOI: 10.1016/j.ymeth.2011.09.020. View

Walker J, Dickson V . The peripheral stalk of the mitochondrial ATP synthase. Biochim Biophys Acta. 2006; 1757(5-6):286-96. DOI: 10.1016/j.bbabio.2006.01.001. View

Assadi-Porter F, Fillingame R . Proton-translocating carboxyl of subunit c of F1Fo H(+)-ATP synthase: the unique environment suggested by the pKa determined by 1H NMR. Biochemistry. 1995; 34(49):16186-93. DOI: 10.1021/bi00049a034. View

Murata T, Yamato I, Kakinuma Y, Leslie A, Walker J . Structure of the rotor of the V-Type Na+-ATPase from Enterococcus hirae. Science. 2005; 308(5722):654-9. DOI: 10.1126/science.1110064. View

10.

Krah A, Pogoryelov D, Meier T, Faraldo-Gomez J . On the structure of the proton-binding site in the F(o) rotor of chloroplast ATP synthases. J Mol Biol. 2009; 395(1):20-7. DOI: 10.1016/j.jmb.2009.10.059. View

11.

Azzi A, Casey R, Nalecz M . The effect of N,N'-dicyclohexylcarbodiimide on enzymes of bioenergetic relevance. Biochim Biophys Acta. 1984; 768(3-4):209-26. DOI: 10.1016/0304-4173(84)90017-x. View

12.

Vagin A, Teplyakov A . Molecular replacement with MOLREP. Acta Crystallogr D Biol Crystallogr. 2010; 66(Pt 1):22-5. DOI: 10.1107/S0907444909042589. View

13.

Pogoryelov D, Yildiz O, Faraldo-Gomez J, Meier T . High-resolution structure of the rotor ring of a proton-dependent ATP synthase. Nat Struct Mol Biol. 2009; 16(10):1068-73. DOI: 10.1038/nsmb.1678. View

14.

. The CCP4 suite: programs for protein crystallography. Acta Crystallogr D Biol Crystallogr. 1994; 50(Pt 5):760-3. DOI: 10.1107/S0907444994003112. View

15.

EPLER J, Shugart L, Barnett W . N-formylmethionyl transfer ribonucleic acid in mitochondria from Neurospora. Biochemistry. 1970; 9(18):3575-9. DOI: 10.1021/bi00820a011. View

16.

Meier T, Krah A, Bond P, Pogoryelov D, Diederichs K, Faraldo-Gomez J . Complete ion-coordination structure in the rotor ring of Na+-dependent F-ATP synthases. J Mol Biol. 2009; 391(2):498-507. DOI: 10.1016/j.jmb.2009.05.082. View

17.

Stoscheck C . Quantitation of protein. Methods Enzymol. 1990; 182:50-68. DOI: 10.1016/0076-6879(90)82008-p. View

18.

Cain B, Simoni R . Proton translocation by the F1F0ATPase of Escherichia coli. Mutagenic analysis of the a subunit. J Biol Chem. 1989; 264(6):3292-300. View

19.

Ostermeier C, Michel H . Crystallization of membrane proteins. Curr Opin Struct Biol. 1997; 7(5):697-701. DOI: 10.1016/s0959-440x(97)80080-2. View

20.

Murshudov G, Vagin A, Dodson E . Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr D Biol Crystallogr. 1997; 53(Pt 3):240-55. DOI: 10.1107/S0907444996012255. View