The Nobel Prize in Chemistry 2003

Peter Agre Roderick MacKinnon

for discoveries concerning channels in cell membranes

"for the discovery of water channels"

"for structural and mechanistic studies of ion channels"

Aquaporin (PDB file: 1IH5)

Sui et al. (2001)Nature 414, 872-876

Models of AQP1, sequence alignment of selected superfamily members and a view of the density map.

De Groot & GrubmüllerScience (2001) 294: 2304-2305

Vista superior (izqda) y lateral (drcha) del tetrámero de acuaporina en una bicapa lipídica

The effective pore diameter (a) and hydrophobicity (b) of theAQP1 and GlpF channels

Sui et al. (2001)Nature 414, 872-876

Side-views 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 & GrubmüllerScience (2001) 294: 2304-2305

Orientación dipolar de las moléculas de agua pasando a través del poro de la acuaporina humana

De Groot & GrubmüllerScience (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 & GrubmüllerScience (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

Jiang et al. (2002) Nature 417, 515-522M. Schumacher & J.P. Adelman (2002) Nature 417, 501 - 502

Gating and opening of a bacterial Ca2+-gated K+ channel

Nature 1 May 2003

FJ Sigworth (2003) Nature 423, 21Jiang et al. (2003) Nature 423, 42-48

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

J. Marx (2002) Science 297, 1252

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

Dutzler et al. (2002) Nature 415, 287-294

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+)

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)

Abramson et al. (2003) Science 301, 610-615

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

Huang et al. (2003) Science 301, 616-620

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

Van den Berg et al. (2004) Nature 427, 36-44

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

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 & GrubmüllerScience (2001) 294: 2304-2305