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The Nobel Prize in Chemistry 2003 Peter AgreRoderick MacKinnon for discoveries concerning channels in cell membranes "for the discovery of water channels"

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Presentation on theme: "The Nobel Prize in Chemistry 2003 Peter AgreRoderick MacKinnon for discoveries concerning channels in cell membranes "for the discovery of water channels""— Presentation transcript:

1 The Nobel Prize in Chemistry 2003 Peter AgreRoderick MacKinnon for discoveries concerning channels in cell membranes "for the discovery of water channels" "for structural and mechanistic studies of ion channels"

2 Aquaporin (PDB file: 1IH5)

3 Sui et al. (2001) Nature 414, Models of AQP1, sequence alignment of selected superfamily members and a view of the density map.

4 De Groot & Grubmüller Science (2001) 294: Vista superior (izqda) y lateral (drcha) del tetrámero de acuaporina en una bicapa lipídica

5 The effective pore diameter (a) and hydrophobicity (b) of the AQP1 and GlpF channels Sui et al. (2001) Nature 414,

6 Side- views of AQP1 Sui et al. (2001) Nature 414,

7 205 moléculas de agua en los alrededores del poro de la acuaporina durante la simulación por Dinámica Molecular De Groot & Grubmüller Science (2001) 294:

8 Orientación dipolar de las moléculas de agua pasando a través del poro de la acuaporina humana De Groot & Grubmüller Science (2001) 294:

9 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:

10 Sucrose-specific porin (PDB code: 1a0s)

11 Canal de Potasio (Ionóforo)..\..\Estructuras\Canal(1BL8).msv

12 Iones de K en el poro..\..\Estructuras\CanalK.msv

13 Nature 30 May 2002

14 Jiang et al. (2002) Nature 417, M. Schumacher & J.P. Adelman (2002) Nature 417, Gating and opening of a bacterial Ca 2+ -gated K + channel

15 Nature 1 May 2003

16 FJ Sigworth (2003) Nature 423, 21 Jiang et al. (2003) Nature 423, 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

17 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

18 Dutzler et al. (2002) Nature 415, 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)

19 Dutzler et al. (2002) Nature 415, 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

20 Dutzler et al. (2002) Nature 415, Cl - selectivity filter and ion binding site

21 Dutzler et al. (2002) Nature 415, Surface electrostatic potential of the dimer forming the chloride channel

22 Dutzler et al. (2002) Nature 415, Two architectures for ion channel proteins: antiparallel (Cl - ) and parallel (K + )

23 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)

24 Abramson et al. (2003) Science 301, Overall structure of lactose/proton symport

25 Abramson et al. (2003) Science 301, Lactose/proton symport Structural changes between inward- and outward-facing conformations

26 Abramson et al. (2003) Science 301, Lactose/proton symport A possible lactose/proton symport mechanism

27 Huang et al. (2003) Science 301, Overall structure of G3P/Pi antiport

28 Huang et al. (2003) Science 301, The G3P/Pi antiport Proposed single–binding site, alternating-access mechanism

29 Van den Berg et al. (2004) Nature 427, A protein-conducting channel General architecture of the SecY complex The hydrophobic pore ring (gold), and plug (green) movement towards the gamma-subunit (magenta)

30 Van den Berg et al. (2004) Nature 427, A protein-conducting channel Different stages of translocation of a secretory protein

31

32 Selectivity filter water molecules and residues forming the hydrophilic face of the channel pore Sui et al. (2001) Nature 414,

33 Residues defining the constriction region Sui et al. (2001) Nature 414,

34 Paso de las moléculas de agua a través del poro de la acuaporina De Groot & Grubmüller Science (2001) 294:


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