molecular basis of membrane transport
DESCRIPTION
Molecular Basis of Membrane Transport. Manoj S. Nair, Ph.D Postodoctoral Fellow, Biochemistry 812 Biosciences bldg, 484 w. 12 th ave Columbus, OH 43210 [email protected]. Outline of Talk. Types of transport across membranes Passive transport Carrier mediated Active transport - PowerPoint PPT PresentationTRANSCRIPT
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MOLECULAR BASIS OF MEMBRANE TRANSPORT
Manoj S. Nair, Ph.DPostodoctoral Fellow,
Biochemistry812 Biosciences bldg, 484 w.
12th aveColumbus, OH 43210
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Outline of Talk Types of transport across membranes1. Passive transport2. Carrier mediated 3. Active transport Nernst equilibrium for ion transport Mechanism of ion transport (K-selectivity
filter) Endocytosis of proteins/protein domains
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Introduction to Cellular Biophysics A. Molecular Basis of Membrane Transport.
Essential Cell Biology Alberts, Bray, et al.
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Fluid mosaic model of membranes
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Dynamic diffusion of lipids in membranes
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Active transport
Transport up a concentration gradient
Uses energy (ATP) May also cause
charge gradient across the membrane causing the molecule to move against the membrane potential.
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Properties of “Active” membrane pumpsATPases (sometimes GTPases)Example of a Na+/K+ pump
Na+/K+ pump uses 30% resting ATP
Active Pumps are used to transport materials against their electrochemical gradient
Essential Cell Biology Alberts, Bray, et al.
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a) Uniport: 1 type of solute is transportedEg: Valinomycin (K+ transport)
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Valinomycin is a carrier for K+. It is a circular molecule, made up of 3 repeats of the sequence shown above.
N C H C OHC
C HC H 3H 3 C
O
C N
C HC H 3H 3 C
OHC
C HC H 3H 3 C
C O C H
C H 3
C
O
H
O
H3
V a lin o m y c in
L -v a l in e D -h y d ro x y - D -v a l in e L - la c t ic i s o v a le r ic a c id a c id
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Valinomycin is highly selective for K+ relative to Na+. The smaller Na+ ion cannot simultaneously interact with all 6 oxygen atoms within valinomycin. Thus it is energetically less favorable for Na+ to shed its waters of hydration to form a complex with valinomycin.
Valinomycin
O O O
O O
Hydrophobic
O
K+
Puckering of the ring, stabilized by H-bonds, allows valinomycin to closely surround a single unhydrated K+ ion. Six oxygen atoms of the ionophore interact with the bound K+, replacing O atoms of waters of hydration.
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Whereas the interior of the valinomycin-K+ complex is polar, the surface of the complex is hydrophobic. This allows valinomycin to enter the lipid core of the bilayer, to solubilize K+ within this hydrophobic milieu.Crystal structure
Valinomycin
O O O
O O
Hydrophobic
O
K+
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Valinomycin is a passive carrier for K+. It can bind or release K+ when it encounters the membrane surface.Valinomycin can catalyze net K+ transport because it can translocate either in the complexed or uncomplexed state.The direction of net flux depends on the electrochemical K+ gradient.
Val Val
Val-K+ Val-K+
K+
membrane
K+
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b) Symport: 2 different solutes transported together in one directionEg: Glucose –Na+ tranporter in epithelial cellsLactose permease: H+ -lactose symport
c)Antiport: 2 different solutes transport in opposite directionsEg: Adenine nucleotide translocase (ATP/ADP exchanger)
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Passive transport: Ion channels & Pores
Properties of transmembrane -helices:
Amphiphilic nature
Designer Peptides of Ser & Leu:Formed a hexamer channel in phospholipid membranes.
S.R.Goodman. 1998
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What is the mechanism for ion selectivity of channels? This is a frontier of biophysics.
With Passive Channels, ions or other substances move DOWN their electrochemical gradient
+ +
+++
-- -
--
-
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Electrochemical Gradient
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Basic structure of the potassium channel. Doyle et al. Science, 1998. Nobel Prize in Chemistry in 2003
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KcsA Selectivity Filter
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KvAP channel voltage sensing paddle
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Avidin detection of voltage using biotinlyated KvAP
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Receptor-activated gate
• “Gated” channels i.e. channels that open in response to physiological stimuli
Essential Cell Biology Alberts, Bray, et al.