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Membrane Proteins.doc

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Biology 2382B
Sashko Damjanovski

Membrane Proteins - carry out the biological functions of membranes - they are all asymmetric Three types of membrane proteins 1. Integral: transmembrane domain (1-extracellular and 1-exoplasmic) 2. Peripheral: bound to a membrane protein (links integral to cytoskeleton) 3. Lipid linked: bound directly to lipids in plasma membrane Integral membrane proteins - asymmetric - contain 3 distinct domains  Cytoplasmic  hydrophilic  Exoplasmic  hydrophilic  Transmembrane  hydrophobic o Secondary/tertiary structure that span the lipid bilayers o α helices (20-25 hydrophobic AA)  Arg and Lys (charged AA) near cytosolic side  Anchoring transmembrane protein (don’t want to enter membrane and interact with hydrophobic tails)  Interact with polar head groups o β barrels  hydrophobic shape that can be a transmembrane domain Lipid-linked Proteins - anchored to membrane by lipophilic adduct (through bonds) Three ways of linking lipid-linked proteins Acylation (cytosolic)  attaching protein to plasma membrane through N terminal glycine residue Prenylation (cytosolic)  attaching protein to plasma through Cys residue at or near C terminal domain Glycosylphophatidylinositol (GPI always exterior)  add sugars and phosphoethanolamine, GPI anchor (protein will not interact with cytoskeleton) Peripheral Proteins • “attached” through non-covalent interactions: – Ionic interactions, hydrogen bonds – Protein-protein interactions – van der Waals forces • Cytoskeletal filaments can associate with bilayer through peripheral proteins Insertions proteins into membranes - Translation occurs in the cytosol! (ribosome is in cytosol) - Translation needs a signal to get it to the membrane - Topogenic sequences: amino acid sequences (structure/shape) - 1) N terminal signal sequence - 2) STA: stops transfer and anchors it to the membrane - 3) SA: internal to the protein (not cleaved) Synthesis of Type I proteins - proteins are made with N terminal first - signal is then recognized and taken to the ER - as protein is being translated, there will be an STA sequence (stop putting it through the translocon) - N terminal is in lumen, C terminal is in cytosol Synthesis of Type II and Type III, IV proteins Type II: Type III: Type IV: orientation of initial helix determined by positively charged amino acids next to signal anchor sequence (charge dependant) - have alternating signal- anchor sequences and stop transfer sequences - can have even or odd number of transmembrane domains - in cytosol: need signal to get to the membrane Topogenic sequences Transport across membranes - Passive diffusion - Facilitated Transport (pores, channels, gates, uniporter) - Active Transport (ATP pumps, anti and symports) Passive diffusion - partition coefficient: measure of the preference of a molecule to partition into a hydrophobic environment (K = c^m/c^aq) - higher K = more lipid soluble - the main determinants of diffusion are the partition coefficient and the concentration difference Facilitated Transport - driving force: concentration gradient - types: pores, channels, gates, uniporters - movement of hydrophilic substances through a protein-lined pathway so they don’t come into contact with hydrophobic interior of membrane - faster than predicted by passive diffusion - saturable and specific I.e. glucose uniporters (GLUT1)  g
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