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The Nobel Prize in Chemistry 2003
for discoveries concerning channels in cell membranes
"for the discovery of water
channels"
Peter Agre
"for structural and mechanistic
studies of ion channels"
Roderick MacKinnon
Aquaporin (PDB file: 1IH5)
Models of
AQP1, sequence
alignment of
selected
superfamily
members and a
view of the
density map.
Sui et al. (2001)
Nature 414, 872-876
Vista superior (izqda) y lateral (drcha) del tetrámero
de acuaporina en una bicapa lipídica
De Groot & Grubmüller
Science (2001) 294: 2304-2305
The effective
pore diameter
(a) and
hydrophobicity
(b) of the
AQP1 and GlpF
channels
Sui et al. (2001)
Nature 414, 872-876
Sideviews of
AQP1
Sui et al. (2001)
Nature 414, 872-876
205 moléculas de agua
en los alrededores del
poro de la acuaporina
durante la simulación
por Dinámica
Molecular
De Groot & Grubmüller
Science (2001) 294: 2304-2305
Orientación dipolar de las
moléculas de agua pasando
a través del poro de la
acuaporina humana
De Groot & Grubmüller
Science (2001) 294: 2304-2305
Representación esquemática del paso de las moléculas de agua a través del poro
de la acuaporina humana (AQP1) y de la gliceroporina bacteriana (GlpF)
De Groot & Grubmüller
Science (2001) 294: 2304-2305
Sucrose-specific porin (PDB code: 1a0s)
Canal de Potasio (Ionóforo)
..\..\Estructuras\Canal(1BL8).msv
Iones de K en el poro
..\..\Estructuras\CanalK.msv
Nature 30 May 2002
Gating and opening of a bacterial Ca2+-gated K+ channel
Jiang et al. (2002) Nature 417, 515-522
M. Schumacher & J.P. Adelman (2002) Nature 417, 501 - 502
Nature 1 May 2003
Voltage sensing in a K+ channel
The control of ion flow through voltage-gated channels is very
sensitive to the voltage across the cell membrane.
By comparison, an electronic device such as a transistor is much less
sensitive to applied voltage
FJ Sigworth (2003) Nature 423, 21
Jiang et al. (2003) Nature 423, 42-48
Sodium channel responsible for
initiating the cardiac action potential
A single amino acid change (red dot) in this large protein may make
people more susceptible to heart arrhytmias
J. Marx (2002) Science 297, 1252
Structure of a chloride channel at 3.0 Å
Stereo view from the extracellular side (a) and side view with the
extracellular solution above (b)
Dutzler et al. (2002) Nature 415, 287-294
Structure of a chloride channel at 3.0 Å
The two halves of the subunut are green and cyan, and regions forming
the Cl- selectivity region are red
Dutzler et al. (2002) Nature 415, 287-294
Cl- selectivity filter and ion binding site
Dutzler et al. (2002) Nature 415, 287-294
Surface electrostatic potential of the
dimer forming the chloride channel
Dutzler et al. (2002) Nature 415, 287-294
Two architectures for
ion channel proteins:
antiparallel (Cl-) and
parallel (K+)
Dutzler et al. (2002) Nature 415, 287-294
Membrane Transporters:
Symporters and Antiporters
•
Use a solute gradient to drive the translocation of other substrates:
ions, sugars, drugs, neurotransmitters, nucleosides, amino acids,
peptides, and other hydrophylic solutes
•
The largest family is the Major Facilitator Superfamily (MFS),
with more than 1000 members identified to date
•
Most MFS proteins have 12 transmembrane alpha-helices
•
The most common substrate translocation mechanism is based on
the alternating-access model, with two major conformations:
inward-facing (Ci) and outward-facing (Co)
Overall structure
of lactose/proton
symport
Abramson et al. (2003) Science 301, 610-615
Lactose/proton symport
Structural changes between inward- and
outward-facing conformations
Abramson et al. (2003) Science 301, 610-615
Lactose/proton symport
A possible lactose/proton symport mechanism
Abramson et al. (2003) Science 301, 610-615
Overall structure of
G3P/Pi antiport
Huang et al. (2003) Science 301, 616-620
The G3P/Pi antiport
Proposed single–binding
site, alternating-access
mechanism
Huang et al. (2003) Science 301, 616-620
A protein-conducting
channel
General architecture of the
SecY complex
The hydrophobic pore ring (gold), and
plug (green) movement towards the
gamma-subunit (magenta)
Van den Berg et al. (2004) Nature 427, 36-44
A protein-conducting
channel
Different stages of
translocation of a
secretory protein
Van den Berg et al. (2004) Nature 427, 36-44
Selectivity filter
water molecules
and residues
forming the
hydrophilic
face of the
channel pore
Sui et al. (2001)
Nature 414, 872-876
Residues
defining the
constriction
region
Sui et al. (2001)
Nature 414, 872-876
Paso de las moléculas de agua a
través del poro de la acuaporina
De Groot & Grubmüller
Science (2001) 294: 2304-2305