BIOL 2021 Lecture Notes - Lecture 9: Copii, Gtpase, Lipid Bilayer
12 May 2018
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Feb 1st (Lecture 9)
Chapter 13
• Coat-recruitment GTPases
• Fig 13-14a Formation of COPII coated vesicle
o Uncoating: Sar1 hydrolyzes GTP to GDP.
o Pops out of membrane, coat is lost.
o Coat-recruitment GTPases are members of a family of monomeric
GTPases. They include the ARF proteins, which are responsible for the
assembly of both COPI and clathrin coats assembly at Golgi membranes,
and the Sar1 protein, which is responsible for the assembly of COPII coats
at the ER membrane. Coat-recruitment GTPases are usually found in high
concentration in the cytosol in an inactive, GDP-bound state. When a
COPII-coated vesicle is to bud from the ER membrane, for example, a
specific Sar1-GEF embedded in the ER membrane binds to cytosolic
Sar1, causing the Sar1 to release its GDP and bind GTP in its place.
(Recall that GTP is present in much higher concentration in the cytosol
than GDP and therefore will spontaneously bind after GDP is released). In
its GTP-bound state, the Sar1 protein exposes an amphiphilic helix, which
inserts into the cytoplasmic leaflet of the lipid bilayer of the ER membrane.
o The coat-recruitment GTPases also have a role in coat disassembly. The
hydrolysis of bound GTP to GDP causes the GTPase to change its
conformation so that its hydrophobic tail pops out of the membrane,
causing the vesicle’s coat to disassemble. Although it is not known what
triggers the GTP hydrolysis, it has been proposed that the GTPases work
like timers, which hydrolyze GTP at slow but predictable rates, to ensure
that vesicle formation is synchronized with the requirements of the
moment. COPII coats accelerate GTP hydrolysis by Sar1, and a fully
formed vesicle will be produced only when bud formation occurs faster
than the timed disassembly process; otherwise, disassembly will be
triggered before a vesicle pinches off, and the process will have to start
again, perhaps at a more appropriate time and place.
• Fig 13-14b Formation of COPII coated vesicle
o Inner coat:
▪ Coat proteins (Sec23 and 24) bind to Sar1.
▪ Cargo receptors bind to adaptor protein.
o GTP-bound Sar1 binds to a complex of two COPII adaptor coat proteins,
called Sec23 and Sec24, which form the inner coat. Sec24 has several
different binding sites for the cytosolic tails of cargo receptors. The entire
surface of the complex that attaches to the membrane is gently curved,
matching the diameter of COPII-coated vesicles.
• Fig 13-14d Formation of COPII coated vesicle
o Outer coat:
▪ More coat proteins bind to Sar1 to make the curvature.
▪ Bud pinches off as vesicles.
• Fig 13-14a Formation of COPII coated vesicle
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