What three ways can membrane proteins attach?
- A groove/polar pocket that binds a lipid or recognises a specific ligand
- An ion binding site
- A shape that is complementary to the membrane, a curved surface of head groups with charges that interact with the membrane
results in peripheral membrane proteins - binding at the periphery and do not penetrate through the membrane
Fun fact!
~50% of surface of synaptic vesicle is proteins
Attachment of peripheral proteins to membranes is permanent. True or False?
False. Different peripheral proteins have differing degrees of transiency; some being more permanently attached than others but still reversible
Describe the binding of ENTH type domains to membranes and give an example protein with this motif.
ENTH motif binds PI(4,5)P2 ligand, more permanent because of a hydrophobic protrusion into the membrane binding a head group - but still can be reverted.
Describe the binding of BAR type domains to membranes and give an example protein with this motif.
BAR motif binds complementary structure to membrane strongly as large surface, e.g. in Amphiphysin, but interactions with ions or exchanging phospholipid head groups can relieve the binding of the domain and the membrane.
Describe the binding of Pleckstrin Homology type domains to membranes and give an example protein with this motif.
PH motifs bind phosphatidyl inositols; PIP2, PIP3 e.g. in PLC.
Describe the binding of C2 type domains to membranes and give an example protein with this motif.
C2 binds Ca2+ and anionic phospholipids, e.g. in PKC
Describe the binding of Ankyrin-repeat type domains to membranes and give an example protein with this motif.
Ankyrin repeat domains bind phosphatidylserine, e.g. Ankyrin
Describe the binding of FERM type domains to membranes and give an example protein with this motif.
FERM domains bind PI(4,5)P2, e.g. in Ezrin, radixin and moesin.
Describe the binding of FYVE type domains to membranes and give an example protein with this motif.
FYVE domains bind PI(3)P e.g. EEA1
Describe the binding of PX type domains to membranes and give an example protein with this motif.
PX domains bind PI(3)P, e.g. sorting nexins
The association of peripheral proteins with membranes is dynamic and depends on what 4 things?
- The type of membrane
- Ca2+ concentration
- Availability of lipid species
- Shape of membrane
What three ways can proteins cause membrane deformation?
- Amphipathic helix - polar and hydrophobic amino acids on opposite sites of helix
- Loop insertion - loops with hydrophobic amino acids
- Curved lattices - lattices form a curved polymer that bind cargo proteins, forming vesicles of tight curvature.
(Or by proteins just binding themselves to complementary regions of the membrane, e.g, BAR domains)
How do proteins become anchored in the membrane?
Through lipidation - addition of a lipid tail to the protein, which is often reversible.
Some lipid anchors are tucked away when the protein is in the cytosol.
Give examples of proteins that are anchored to the membrane through lipidation.
G-proteins, C-terminus of GPCRs, SNAREs… etc.
Give 3 examples of lipidation modifications allowing proteins to be anchored to a membrane.
- Palmitoyl group on internal Cys or Ser
- N-Myristoyl group on amino-terminal Gly
- Farnesyl or Geranygeranyl group on carboxyl-terminal Cys
These lipid modifications result in the protein being tucked on the inside facing the cytosolic environment
What are GPI anchors?
GPI = Glycosylphosphatidylinositol
A phosphoglyceride attached to the C-terminus of a protein during post-translational modification anchoring of proteins to plasma membranes.
The phosphate connects glycerol to an inositol group, which is attached to sugars, e.g. GlcNAc, Mannose chain. Attaches to protein by phosphate at C-terminus.
Where are GPI anchors found?
Exclusively in plasma membranes and primarily in lipid rafts, facing outside of the cell
Where are GPI-anchors synthesised?
In the ER and Golgi
What are integral membrane proteins?
AKA Transmembrane/TM proteins, are proteins that cross the membrane.
How are integral membrane proteins different from peripheral and GPI-anchored proteins?
Peripheral and GPIs can be cleaved and then become soluble to be released from the membrane. TM proteins cannot.
Also cannot be removed because of a hydrophobic helix which would not be stable outside the membrane environment.
How many types of TM proteins are there?
4
Describe the structure of Type I transmembrane proteins.
A single transmembrane domain;
C-terminus of protein is in cytosol.
N-terminus is facing extracellular environment, or lumen of intracellular compartments.
Describe the structure of Type II transmembrane proteins.
A single transmembrane domain;
N-terminus is in cytosol
C-terminus is facing extracellular environment/lumen of intracellular compartments
