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Molecular Basis of Membrane Transport. Manoj S. Nair, Ph.D Postodoctoral Fellow, Biochemistry 812 Biosciences bldg, 484 w. 12 th ave Columbus, OH 43210 Nair.30@osu.edu. Outline of Talk. Types of transport across membranes Passive transport Carrier mediated Active transport

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molecular basis of membrane transport

Molecular Basis of Membrane Transport

Manoj S. Nair, Ph.D

Postodoctoral Fellow, Biochemistry

812 Biosciences bldg, 484 w. 12thave

Columbus, OH 43210

Nair.30@osu.edu

outline of talk
Outline of Talk
  • Types of transport across membranes
  • Passive transport
  • Carrier mediated
  • Active transport
  • Nernst equilibrium for ion transport
  • Mechanism of ion transport (K-selectivity filter)
  • Endocytosis of proteins/protein domains
slide3

Introduction to Cellular Biophysics

A. Molecular Basis of Membrane Transport.

Essential Cell Biology Alberts, Bray, et al.

slide6

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.
slide7

Properties of “Active” membrane pumps

Example of a Na+/K+ pump

ATPases (sometimes GTPases)

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.

slide8

a) Uniport: 1 type of solute is transported

Eg: Valinomycin (K+ transport)

slide9
Valinomycin is a carrier for K+.

It is a circularmolecule, made up of 3 repeats of the sequence shown above.

slide10

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.

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.

slide11
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

slide12
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.

slide13

b) Symport: 2 different solutes transported together in one direction

Eg: Glucose –Na+ tranporter in epithelial cells

Lactose permease: H+ -lactose symport

c)Antiport: 2 different solutes transport in opposite directions

Eg: Adenine nucleotide translocase (ATP/ADP exchanger)

passive transport ion channels pores
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

slide16

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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slide20

Basic structure of the potassium channel.

Doyle et al. Science, 1998. Nobel Prize in Chemistry in 2003

slide24

“Gated” channels i.e. channels that open in response to physiological stimuli

Receptor-activated gate

Essential Cell Biology Alberts, Bray, et al.