interacciones proteína - proteína

InteraccionesProteína - Proteína

Fuertes (t = s, min) Complejos proteicos (estables)

Débiles (t = s, ms)Complejo intermediario (transitorio)en una reacción enzimática

Schwikowski et al.(2000) Nature Biotech. 18, 1257 - 1261

Interactions between functional groups

Interactions between proteins of different compartments

Schwikowski et al.(2000) Nature Biotech. 18, 1257 - 1261

Tong et al. (2002) Science 295, 321-324

Yeast SH3 domains — which recognize proline-rich peptides — generated a network containing 394 interactions among 206 proteins

An interaction map of the yeast proteome assembled from published interactions

Schwikowski et al.(2000) Nature Biotech. 18, 1257 - 1261

..\..\LINKS\Ho Nature(2002).pdf

Ho et al. (2002) Nature 415, 180

Protein network in Saccharomyces cerevisiae

Kumar & Snyder (2002) Nature 415, 123-124Ho, Y et al. (2002) Nature 415, 180 - 183

Analysing protein interactions:Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry

T. Iiri et al. (1998) Nature 394, 35-38

How does a trimeric G protein on the inside of a cell membrane respond to activation by a transmembrane receptor?

Trimeric () G proteins relay signals from transmembrane receptors to intracellular enzymesand ion channels, thereby mediating vision, smell, taste and the actions of many hormones andneurotransmitters

T. Iiri et al. (1998) Nature 394, 35-38

The GTPase cycle of trimeric G proteins

The 'turn-on' step begins when the activated receptor (R*) associates with the trimer of (GDP), causing dissociation of GDP. Then GTP binds to the complex of R* with the trimer in its 'empty' state (e), and the resulting GTP-induced conformational change causes GTP to dissociate from R* and from . After the 'turn-off' step (hydrolysis of bound GTP to GDP and inorganic phosphate, Pi), GDP reassociates with .

T. Iiri et al. (1998) Nature 394, 35-38

Contacts between G (left) and G-GDP (right)

Red dashed lines indicate contacts that appear to be required for receptor activation but not for G–G association; green dashed lines indicate contacts that are important for both functions

T. Iiri et al. (1998) Nature 394, 35-38

How does a trimeric G protein on the inside of a cell membrane respond to activation by a transmembrane receptor?

Biomedical relevance:G-protein mutations in patients with hypertension and inherited endocrine disorders enhance or block signals from stimulated receptors.

A. Chiarugi & M.A. Moskowitz (2002) Science 297, 200

PARP-1: A Perpetrator of Apoptotic Cell Death

Apoptotic cell death is triggered by activation of the nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1).

Through unknown mechanisms, PAR formation and NAD+ depletion may trigger a cascade of events.

PS II

h

e

e*

cyt b6-fcomplex

OUT

IN

H2O

QPS I

h

e

e*

Pc (Cu )+

cyt c6 (Fe )2+

Fd

Navarro et al. (1997) J. Biol. Inorg. Chem. 2, 11-22

Cyt c6Pc

PS I

b6f

PSI-driven Electron Transfer

Fdlight

CytPc

From Cytochrome c6 to Plastocyanin

II IIII

II IIII

Navarro et al. (1997) J. Biol. Inorg. Chem. 2, 11-22

PROKARYOTES

Time (109 years ago)4 3 2 1 0

Atm

osph

eric

Lev

el(f

ract

ions

of 2

1% v

/v)

0.001

0.01

0.1

1

(Adapted from Peschek, 1996)

Oxygen content of the earth's atmosphere

EUKARYOTESPhotosyntheticO2 production

Pasteur Point(O2 respiration)

Berkner-Marshall Point(Terrestrial life)

Cu

FeS2-

SO42-

Time (109 years ago)4 3 2 1 0

Ava

ilabi

lity

(Adapted from Williams & Silva, 1997)

Plastocyanin

Cu ligands:His-35 Cys-84 His-87 Met-92

Heme ligands:His-19 Met-61

Cytochrome c6

___________________________________________________

Organism Protein pI___________________________________________________

Spinach Plastocyanin 4.2

Monoraphidium Plastocyanin 3.7 Cytochrome c6

3.6

Anabaena Plastocyanin 9.0 Cytochrome c6

9.0

Synechocystis Plastocyanin 5.5 Cytochrome c6 5.6

____________________________________________________

Isoelectric point of cytochrome c6 and plastocyaninisolated from different organisms

Cytochrome c6

Plastocyanin

De la Rosa et al. (2002) Bioelectrochemistry 55, 41-45

Photosyntheticorganisms growingunder controlledconditions

A

= 2

x 10

-3

Spinach PC

Monoraphidium PC

Monoraphidium Cyt c6

Anabaena PC

Synechocystis PC

200 s

200 s

200 s

7 ms

500 s

A =

2 x

10-3

Routes

c: 1 2 3 3' 4hb: 1 2 2' 3' 4ha: 1 1' 2' 3' 4h

Protred + PSIred1

[Protred ... PSIred]*KR

3

Protox + PSIred

ket

4

[Protred ... PSIox]*

h

3'Protred + PSIox [Protred ... PSIox]

h h

K'RK'A

1' 2'

[Protred ... PSIred]KA

2

De la Rosa et al. (2002) Bioelectrochemistry 55, 41-45

KINETIC TYPES FOR THE REACTION MECHANISM

Type I

Protred + PSIox Protox + PSIred

Type II

Protred + PSIox [Protred ... PSIox] Protox + PSIred

Type III

Protred + PSIox [Protred ... PSIox] [Protred ... PSIox]* Protox + PSIred

KINETIC TYPES FOR THE REACTION MECHANISM

Type I

Protred + PSIox Protox + PSIred

Type II

Protred + PSIox [Protred ... PSIox] Protox + PSIred

Type III

Protred + PSIox [Protred ... PSIox] [Protred ... PSIox]* Protox + PSIred

KINETIC TYPES FOR THE REACTION MECHANISM

Type I

Protred + PSIox Protox + PSIred

Type II

Protred + PSIox [Protred ... PSIox] Protox + PSIred

Type III

Protred + PSIox [Protred ... PSIox] [Protred ... PSIox]* Protox + PSIred

KINETIC TYPES FOR THE REACTION MECHANISM

Type I

Protred + PSIox Protox + PSIred

Type II

Protred + PSIox [Protred ... PSIox] Protox + PSIred

Type III

Protred + PSIox [Protred ... PSIox] [Protred ... PSIox]* Protox + PSIred

Navarro et al. (1997) J. Biol. Inorg. Chem. 2, 11-22

Flexibilidad estructural de la plastocianina