1. Interacciones Lípidos - Proteínas

2. Serum albumin is the carrier of fatty acids in the blood. Serum albumin is the most plentiful protein in blood plasma. Each protein molecule can carry seven fatty acid molecules. When our body needs energy or needs building materials, fat cells release fatty acids into the blood. There, they are picked up by serum albumin and delivered to distant parts of the body. Interacciones Lípidos - Proteínas Serum albumin http://www.rcsb.org/pdb

3. Interacciones Lípidos - Proteínas Proteínas de membrana MEMBRANE PROTEINS OF KNOWN STRUCTURE http://www.mpibp-frankfurt.mpg.de/michel/public/memprotstruct.html

4. Dominios Básicos de Estructura Secundaria en las Proteínas de Membrana Bacteriorrodopsina (hélices  ) Porina (Cadenas  )

5. O 2 The mitochondrial respiratory chain Claudio Gomes - ITQB, Oeiras, Portugal

6. Complex I NADH:quinone oxidoreductase Mitochondria 42/43 subunits / ~ 900 kDa Cofactors: 1-2 FMN, 7-8 FeS Covalently bound lipid ~ 3 bound quinol molecules Proton translocation Prokaryotic 14 subunits / ~500 MDa ~ 55 TM helices Cofactors: 1 FMN, up to 9 FeS Claudio Gomes - ITQB, Oeiras, Portugal

7. Complex II succinate:quinone oxidoreductase Mitochondria 4 subunits 1 FAD covalently bound FeS clusters ([2Fe-2S]; [4Fe-4S], [3Fe- 4S]) 2 TM segments containing heme b Prokaryotic Identical to the mitochondrial complex except at the TM / heme b composition Claudio Gomes - ITQB, Oeiras, Portugal

8. Complex III quinol:cytochrome c oxidoreductase Mitochondria 11 subunits / dimer / ~240 kDa Three core subunits Contains up to 8 additional subunits Cofactors: 2 cyt b, cyt c 1, Rieske [2Fe-2S] H + translocation (  Q-cycle mechanism) Prokaryotic 3 core subunits and cofactors present Claudio Gomes - ITQB, Oeiras, Portugal

9. Z. Zhang et al (1998) Nature 392, 677-684 The b-c 1 complex – Complex III

10. http://www.life.uiuc.edu/crofts/bc-complex_site/ Electron-Proton Transfer in Complex III

11. Complex IV cytochrome c : oxygen oxidoreductase Mitochondria 13 subunits (3 core) Binuclear Cu A site, heme a, Heme-copper site Cu A -a 3 197919901995 Claudio Gomes - ITQB, Oeiras, Portugal

12. Cytochrome c oxidase – Complex IV Cytochrome Oxidase Home Page http://www-bioc.rice.edu/~graham/CcO.html Subunit III (in blue) with an embedded phospholipid. Subunit IV (green, unique to this enzyme) Subunit I (yellow) - Subunit II (purple) Antibody fragment (cyan) used to drive crystallization.

13. Complex IV cytochrome c : oxygen oxidoreductase Mitochondria 13 subunits (3 core) Binuclear Cu A site, heme a, Heme-copper site Cu A -a 3 Prokaryotic 3-5 subunits (including core sub I-III) Multiple heme types (e.g. A, A s, B, O) Proton pumps Superfamily of heme-copper oxidases Claudio Gomes - ITQB, Oeiras, Portugal

14. Terminal Oxidases Diversity H + b Cu B o 3 O2O2 H2O H2O Quinol oxidases (eg. bo 3 Ec) H + b Cu B b 3 O2O2 H2O H2O FixN-type oxidases (eg. cbb 3 Pd) b d b Cytochrome bd (eg. bd Ec) Fe Alternative oxidase (eg. plant mitochondria) Heme-copper oxidases H + a Cu B a 3 A O2O2 H2O H2O Cytochrome oxidases (eg. aa 3 Pd) Non heme-copper oxidases Claudio Gomes - ITQB, Oeiras, Portugal

15. Aerobic metabolism is more efficient Aerobic Bacteria The endosymbiotic theory suggests that eukaryotes acquired respiration capability by the symbiosis with an oxygen respiring bacteria Ancestral anaerobic eukaryote Aerobic Eukaryote Some bacterial genes move to the nucleus and the bacterial endosymbionts become mitochondria Non-photosynthetic Eukaryote Endosymbion ts become mitochondria Photosynthetic cyanobacterium New cell can make ATP from sunlight Claudio Gomes - ITQB, Oeiras, Portugal

16. Mitochondrial oxidative phosphorylation http://www.life.uiuc.edu/crofts/bioph354/lect8.html Biophysics 354, Lecture 8 Complex I Complex II Complex III Complex IV ATPase

17. Cambridge University Robert Poole F0F0 F0F0 H+H+ H+H+ Respiratory chain + + - - Inter- Membrane space Inter- Membrane space Inner membrane Matrix F1F1 F1F1 H+H+ H+H+ ADP + P i ATP + H 2 O

18. Cambridge University Robert Poole

19. Cambridge University Robert Poole

20. Cambridge University Robert Poole HOW MUCH ATP DO WE PRODUCE? AT REST Adult converts one half body weight equivalent of ATP per day AT REST Adult converts one half body weight equivalent of ATP per day NORMAL Adult converts body weight equivalent of ATP per day NORMAL Adult converts body weight equivalent of ATP per day HARD WORK Adult converts up to 1000 kg ATP per day HARD WORK Adult converts up to 1000 kg ATP per day 1000 kg 70kg? £1M?

21. Los Elementos y Moléculas de la Vida Losada, Vargas, Florencio y De la Rosa (1998-9) Editorial Rueda, Madrid

22. Schnitzer (2001) Nature 410, 878 - 881 ATP synthase — energy converter.

23. W. Junge et al. (1997) TIBS 22, 420-423 Rotational mechanism of ATP synthase

24. Abrahams et al. (1994) Nature 370, 621-628. viewed from the cytoplasmatic side EE EE  TP  TP  DP  DP ADP + Pi ATP ADP + Pi ATP O O OT T T L L L Energy Structure of F 1 from bovine heart mitochondria

25. Animation of ATP synthesis by F 0 F 1 complexes

26. Animation of ATP-driven  subunit rotation

27. http://www.life.uiuc.edu/crofts/bioph354/lect10.html ATP synthase Animation of the complete mechanism Lecture 10, ATP synthase

28. Yasuda et al (2001) Nature 410, 898-904 Observation of F1 rotation

29. Bacteriorhodopsin

30. Subramaniam & Henderson (2000) Nature 406, 653 - 657 The light-induced all-trans to 13-cis isomerization of the retinal results in deprotonation of the Schiff base followed by alterations in protonatable groups within bacteriorhodopsin. Displacement of Schiff base on deprotonation Observed conformations of retinal derivatives

31. Sass et al. (2000) Nature 406, 649 - 653 Details of the structural differences between the ground state (purple) and the M2 intermediate (yellow). Extracellular viewCytoplasmic view

32. Kühlbrandt (2000) Nature 406, 569 - 570 Molecular mechanism of proton (H + ) pumping in bacteriorhodopsin

33. Spudich JL (2002) Science 288, 1358-9 The four archaeal rhodopsins in H. salinarum

34. Béjà et al. (2000) Science 289, 1902-1906 Phylogenetic analysis of proteorhodopsin with archaeal and Neurospora crassa (NOP1) rhodopsins

35. X. Gomis & M. Coll, Diario de Sevilla, 15 Marzo 2001 Conjugación bacteriana: Transferencia de plásmido con resistencia a un determinado antibiótico

36. Bacterias resistentes a los antibióticos A. Vila, Diario de Sevilla, 10 Julio 2001

37. Bacteria de la tuberculosis. Uno de los muchos microorganismos que ha desarrollado inmunidad frente a los fármacos

38. A. Vila, Diario de Sevilla, 10 Julio 2001 El anillo de beta-lactama

39. A. Vila, Diario de Sevilla, 10 Julio 2001 Beta-lactamasa. Metaloproteína de cinc que destruye a los antibióticos

40. The bacterial conjugation protein TrwB resembles ring helicases and F1-ATPase Gomis et al. (2001) Nature 409, 637-641

41. The bacterial conjugation protein TrwB resembles ring helicases and F1-ATPase Gomis et al. (2001) Nature 409, 637-641 Lateral view View along the 6-fold axis

42. S Murakami et al. (2002) Nature 419,587 Bacterial multidrug efflux transporter

43. S Murakami et al. (2002) Nature 419,587 Bacterial multidrug efflux transporter  The emergence of bacterial multidrug resistance is an increasing problem in the treatment of infectious diseases. Multidrug resistance often results from the overexpression of a multidrug efflux system.  AcrB is a major multidrug exporter in Escherichia coli. It cooperates with a membrane fusion protein, AcrA, and an outer membrane channel, TolC.  Substrates translocated from the cell interior through the transmembrane region and from the periplasm through the vestibules are collected in the central cavity and then actively transported through the pore into the TolC tunnel.  The AcrB system extrudes cationic, neutral and anionic substances, and pumps out some beta-lactams with multiple charged group. AcrAB catalyses efflux driven by proton motive force.