Membrane channels

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Gating-by-Tilt Mechano-sensitivity of
Biomembrane transport
Pierre Sens Institut Curie - Paris. France
Institut Charles Sadron - Strasbourg. France
Matthew Turner Warwick University. England
APS - March 2004 - Montreal
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Membrane Transport Proteins
20 of identified genes in E-Coli are associated
with membrane transport processes
Very important for the cell
Types of transport
Outline of the Talk New gating mechanism for
mechano-sensitive channels Membrane tension
influences (may inhibit ?) transport
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Mechano-sensitive channels
Function osmotic regulation
Structure Two states
Open
Closed
Traditional picture
New picture
Influence of Membrane Tension
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Active Transport
Very asymmetric ionic concentrations
Function creates/maintains concentration
gradients Requires Energy consumption (ATP
hydrolysis - use of ionic gradient)
Examples that involve a structural change
For some transporters, it involves A change of
protein tilt
Membrane tension influences transport rate
Protein Tilt -gt Membrane Energy -gt Protein
Conformation Energy
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Origin of Membrane Energy
Membrane displacement (small)
Energy (Helfrich - 70s)
Bending rigidity vs. Membrane tension
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Mechano-sensitive channels
Example MsCl
Chang Science, 1998 (side)
K. Schulten (top)
K Channel (M. Sansom)
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2-state model ( possible intermediate,
metastable states)
Bottom view
closed
open
Channel
ENERGY
(2)
(1)
Energy barriers
Energy difference
states
Membrane
Energy difference decreases with tension
Total Energy
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High (membrane) Gating energy High Channel
Sensitivity
Membrane contribution to the energy
Traditional picture
New picture
Gating-by-tilt
Requires large dilation for high sensitivity
Adds to (dominates) the sensitivity
Channel size
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New Feature of Gating-by-Tilt !
Effect of Membrane asymmetry
Reduction of tension (bad for gating-by-dilation)
Increase of spontaneous curvature (good for
gating-by-tilt)
Channel opening by asymmetrical lipid addition
Observed in vitro (by EPR spectroscopy) Perozo
Nature Struct. Biol. 9, 696 (2002)
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MEMBRANE TRANSPORT
Locher, Bass, Rees, Science 301, 603 (2003)
Active transport (uses ion gradient)
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Active transition
2-State model
(0)
(2)
Passive (thermal) transition
(1)
-p/4 -p/6 -p/12 0 p/12
p/6 p/4
Involves a change of protein tilt
Membrane energy
May destabilize the metastable state and inhibit
membrane transport
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Summary
Physical consequences of tilted protein
conformation
Membrane tilt may have a dominant contribution to
the gating energy of mechano-sensitive channels
Gating-by-Tilt explains the channel sensitivity
to membrane asymmetry
Membrane elasticity plays an important role in
Active transport
Active transport may - too - be
mechano-sensitive And may be inhibited under high
membrane tension
M.S. Turner P. Sens. Gating-by-tilt of
mechanosensitive membrane channels.
cond-mat/0311574
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pierre.sens_at_curie.fr http//perso.curie.fr/Pierre.
Sens/
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(No Transcript)
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hydrophilic
hydrophobic
Cell membrane are composed of amphiphilic
molecules which self-assemble into fluid bilayers
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Mechano-sensitive channels
Example MsCl
Sukharev Nature 409, 771 (2001)
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Patch clamp measurements

• Open area from conductivity
• Energy DG estimated from
• open area x tension

Frans Maathuis, York
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Corresponding tilt angles
q
Channel q100 (degrees) 100 of gating DGdilate q10 (degrees) 10 of gating DGdilate
MscL 39 12
MscS 24 8
MscA1 21 7
MscA2 31 10
MscMJ 16 5
MscMJR 35 11