membranes part 2 proteins - pumps. membrane proteins integral proteins – transmembrane domains 25...
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Membranes Part 2
Proteins - Pumps
Membrane Proteins• Integral proteins– Transmembrane
domains• 25 aa -helix• -barrel• H-bonding of all amino &
carbonyl groups• Hydrophobic residues
– G, A, L, I, V
– Hydropathy calculations predict TM domains from protein sequence
Membrane Proteins• Peripheral proteins– Acylation
• Farnesylation• Myristoylation• Palmitoylation
– GPI anchor– Electrostatic interaction– Partial insertion– Association with integral protein
Transport Complexes
Control of Membrane Permeability
• Selective permeability of membranes• Control of solute movement across membranes– Pumps
• "active transport"• Require energy source to achieve movement
– Carriers• "passive transport"• Movement of particles down concentration gradients result in
conformational changes that can allow transport against gradient– Channels
• "selective passive transport"• Opening and closing is regulated
Types of Membrane PumpsEnergy Source Pump Substance Distribution
Light
Bacteriorhodopsin H+
HalobacteriaHalorhodopsin Cl-
Photoredox H+ Photosynthetic organisms
Redox potentialElectron transport chain NADH oxidase
H+ Mitochondria, bacteria
Decarboxlyation Ion-transporting decarboxlyases
Na+ Bacteria
Pyrophosphate H+-pyrophosphatase H+ Plant vacuoles, fungi, bacteria
ATP Transport ATPasesvarious
ionsUniversal
Three Families of Transport ATPases
Class Distribution Substrate Functions
F-type Bacteria, chloroplast H+ ATP synthesis or
mitochondria ATP driven H+ pumping
V-type Archaea, eukaryotic H+ ATP driven H+ pumping
membranes
P-type Plasma memb, ER Na, K, Ca Cation pumping
ABC Plasma membrane Various Solute transport
Copyright 2008 by Saunders/Elsevier. All rights reserved.
Figs. 8-5, 8-7, 8-9
Three Families of Transport ATPases
F-type ATPase P-type ATPase ABC transporter
Copyright 2008 by Saunders/Elsevier. All rights reserved.
ATP-Driven PumpsPump Distribution Substrate 1 Function
F0F1 Mitochondria, chloroplasts, bacteria, plasma membranes
H+ ATP synthesis
V0V1 eukaryotic endomembranes H+ ATP-driven H+ pumping
Na/K-ATPase plasma membrane 3 Na+ for 2 K+ Na/K gradient generation
H/K – ATPase stomach & kidney cell plasma membranes
1 H+ for 1 K+ gastric & renal H secretion
H-ATPase plasma membrane in yeast, plants & protozoa
1 H+ proton gradient
CFTR respiratory & pancreatic epithelial cell plasma membranes
ATP, Cl- Cl- secretion
MDR1 Plasma membrane Drugs
MDR2 Liver apical membrane PC Flippase, bile secretion
F and V family ATPases
Subcellular Distribution of F-type and V-type ATPases
Fig. 1.2Copyright 2008 by Saunders/Elsevier. All rights reserved.
P-type ATPase: Ca2+ of the endoplasmic reticulum
Fig. 8-7
Copyright 2008 by Saunders/Elsevier. All rights reserved.
Mechanism of the P-type Ca-pump
Fig. 8-8Copyright 2008 by Saunders/Elsevier. All rights reserved.
ABC Transporters
Pump Distribution Substrate Functions
MDR1 Plasma membrane Organics, drugs Drug secretion
MDR2 Liver plasma membrane Phosphatidylcholine Flippase
CFTR Respiratory, pancreas PM ATP, Cl- Cl- secretion
TAP1, 2 ER Antigenic peptides ER/cytoplasm transport
HisQMP Bacterial PM Histidine Histidine uptake
PstSCAB Bacterial PM Phosphate Phosphate uptake
OppDFBCA Bacterial PM Oligopeptides Peptide uptake
Copyright 2008 by Saunders/Elsevier. All rights reserved.
ABCs of ABC Transporters
• ATP Binding Cassette• Walker A motif or P-loop– GXXGXGKS/T– Binds PO4
• Walker B motif– GX6-84D
– Binds Mg2+
Figs. 8-9 and 8-10
ABC transporters: variations on a common theme
Vitamin B12 transporter BtuC BtuD
Copyright 2008 by Saunders/Elsevier. All rights reserved.
Crystal structure & proposed mechanism of the BtuCD vitamin B12 ABC transporter
Fig. 8-10
Copyright 2008 by Saunders/Elsevier. All rights reserved.
Multiple drug resistance of human tumors from over expression of MDR ABC transporter
Fig. 8-11
Copyright 2008 by Saunders/Elsevier. All rights reserved.