interacciones lípidos - proteínas

InteraccionesLípidos - Proteínas

• 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

InteraccionesLípidos - Proteínas

Proteínas de membrana

MEMBRANE PROTEINS OF KNOWN STRUCTURE

http://www.mpibp-frankfurt.mpg.de/michel/public/memprotstruct.html

http://www.mpibp-frankfurt.mpg.de/michel/public/memprotstruct.html

Dominios Básicos de Estructura Secundaria en las Proteínas de Membrana

Bacteriorrodopsina(hélices )

Porina(Cadenas )

H+H+H+

NADH NAD++ H+

succinatefumarate + 2H+

FAD

FeS

2e-

2e- UQ

UQH2

a CuBa3

FMN

Fe-S

FeS

bH

bL

CuA

Mitochondria

Complex INADH:quinoneoxidoreductase

Complex IIsuccinate:quinone

oxidoreductase

Complex IIIquinol:cytochrome c

oxidoreductase

Complex IVcytochrome c: oxygen

oxidoreductase

2O2 + H2 2H2O O2

The mitochondrial respiratory chain

H+H+H+

NADH NAD++ H+

succinatefumarate + 2H+

FAD

FeS

2e-

2e- UQ

UQH2

a CuBa3

FMN

Fe-S

FeS

bH

bL

CuA

Mitochondria

Complex INADH:quinoneoxidoreductase

Complex IIsuccinate:quinone

oxidoreductase

Complex IIIquinol:cytochrome c

oxidoreductase

Complex IVcytochrome c: oxygen

oxidoreductase

2O2 + H2 2H2O

Claudio Gomes - ITQB, Oeiras, Portugal

Complex INADH: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


Complex IIsuccinate: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


Complex IIIquinol:cytochrome c oxidoreductase

Mitochondria• 11 subunits / dimer / ~240 kDa• Three core subunits • Contains up to 8 additional subunits• Cofactors: 2 cyt b, cyt c1, Rieske

[2Fe-2S]• H+ translocation ( Q-cycle

mechanism)

Prokaryotic • 3 core subunits and cofactors

present


Z. Zhang et al (1998) Nature 392, 677-684

The b-c1 complex – Complex III

http://www.life.uiuc.edu/crofts/bc-complex_site/

Electron-Proton Transfer in Complex III


















Complex IVcytochrome c : oxygen

oxidoreductase

Mitochondria• 13 subunits (3 core) • Binuclear CuA site, heme a,

Heme-copper site CuA-a3

1979 1990 1995


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.







Complex IVcytochrome c : oxygen

oxidoreductase

Mitochondria• 13 subunits (3 core) • Binuclear CuA site, heme a,

Heme-copper site CuA-a3

Prokaryotic • 3-5 subunits (including core sub I-III)• Multiple heme types (e.g. A, As, B, O) • Proton pumps • Superfamily of heme-copper

oxidases


Terminal Oxidases Diversity

H+

b CuB

o3

O2

H2O

Quinol oxidases(eg. bo3 Ec)

H+

b CuBb3

O2

H2O

FixN-type oxidases

(eg. cbb3 Pd)

b db

Cytochrome bd(eg. bd Ec)

Fe Fe

Alternative oxidase(eg. plant mitochondria)

Heme-copper oxidases

H+

a CuB

a3

CuA

O2

H2OCytochrome

oxidases(eg. aa3 Pd)

Non heme-copper oxidases


Aerobic metabolism

is more efficient

AerobicBacteria

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

Endosymbionts become mitochondria

Photosynthetic cyanobacterium

New cell can make ATP from sunlight


Mitochondrial oxidative phosphorylation

http://www.life.uiuc.edu/crofts/bioph354/lect8.htmlBiophysics 354, Lecture 8

Complex IComplex II

Complex III Complex IVATPase

http://www.life.uiuc.edu/crofts/bioph354/lect8.html




CambridgeUniversity

RobertPoole

F0F0

H+H+

Respiratory chainRespiratory chain

++ --

Inter-Membrane

space

Inter-Membrane

space Inner membraneInner membrane MatrixMatrix

F1F1

H+H+

ADP + PiADP + Pi

ATP + H2OATP + H2O

CambridgeUniversity

RobertPoole

CambridgeUniversity

RobertPoole

HOW MUCH ATPDO WE PRODUCE?HOW MUCH ATPDO WE PRODUCE?

AT RESTAdult converts one half body weight equivalent of ATP per day

AT RESTAdult converts one half body weight equivalent of ATP per day

NORMALAdult converts body weight equivalent of ATP per day

NORMALAdult converts body weight equivalent of ATP per day

HARD WORKAdult converts up to 1000 kg ATP per day

HARD WORKAdult converts up to 1000 kg ATP per day

1000 kg

70kg? £1M?70kg? £1M?

ATP S INTASA

Los Elementos y Moléculas de la VidaLosada, Vargas, Florencio y De la Rosa (1998-9)Editorial Rueda, Madrid

Schnitzer (2001) Nature 410, 878 - 881

ATP synthase — energy converter.

W. Junge et al. (1997) TIBS 22, 420-423

Rotational mechanism of ATP synthase

Abrahams et al. (1994) Nature 370, 621-628.

viewed from the cytoplasmatic side

EE

TP

TP

DP

DP

ADP + Pi

ATP

ADP + Pi ADP + Pi

AD

P + P

i

AD

P + P

i

ATPA

TP

O

O OT T T

L L

L

Energy

Structure of F1 from bovine heart mitochondria

Animation of ATP synthesis by F0F1 complexes

Animation of ATP-driven subunit rotation


ATP synthaseAnimation of the complete mechanism

Lecture 10, ATP synthase




Yasuda et al (2001) Nature 410, 898-904

Observation of F1 rotation

Bacteriorhodopsin

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 withinbacteriorhodopsin.

Displacement of Schiff base on deprotonation

Observed conformations of

retinal derivatives

Sass et al. (2000) Nature 406, 649 - 653

Details of the structural differences between the ground state (purple) and the M2 intermediate (yellow).

Extracellular view Cytoplasmic view

Kühlbrandt (2000) Nature 406, 569 - 570

Molecular mechanism of proton (H+) pumping in bacteriorhodopsin

Spudich JL (2002) Science 288, 1358-9

The four archaeal rhodopsins in H. salinarum

Béjà et al. (2000) Science 289, 1902-1906

Phylogenetic analysis of proteorhodopsin with archaeal and Neurospora crassa (NOP1) rhodopsins

X. Gomis & M. Coll, Diario de Sevilla, 15 Marzo 2001

Conjugación bacteriana: Transferencia de plásmido con resistencia a un determinado antibiótico

Bacterias resistentes a los antibióticos

A. Vila, Diario de Sevilla, 10 Julio 2001


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


El anillo de beta-lactama


Beta-lactamasa. Metaloproteína de cinc que destruye a los antibióticos

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

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

Lateral view

View along the 6-fold axis

S Murakami et al. (2002) Nature 419,587

Bacterial multidrug efflux transporter

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.

N N NN N H N HH N H N

N H

N H N H

N H3

3 3

3+

+ +

+

C O OC O OC O OC O O --

--

( h i s t i d i n a s p a r a l e l a s ) ( h i s t i d i n a s p e r p e n d i c u l a r e s )

CITO CRO M O -559 TRANS M E M B RANA Lb

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