PHIL 2015 Chapter Notes - Chapter 9.3: Nicotinic Acetylcholine Receptor, Integral Membrane Protein, Disulfide
23 May 2020
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subunit composition
In the closed state, the kink in the centre of each M2 helix points inward, constricting the
passageway. In the absence of ligand (Ach for nicotinic and GABA for GABA), the C loop
is in an open and uncapped conformation. When the ligand binds, the C loop bends and
caps the occupied binding site, by interdigitating and forming a disulphide bridge with the
adjacent C loop, which results in a conformational change that moves the linker away from
the pore and widening it. The pore can now allow the movement of ions to pass through.
Distinct allosteric sites exist which allows for the modification of activity and cytoplasmic
determinants also control the magnitude of ion flow.
2.4) discuss the diversity of subunit composition of these channels and the potential
significance of this subunit heterogeneity.
Heterogeneity refers to the many receptor subtypes of the nicotinic acetylcholine and
GABA receptors. The different subtypes and locations of expression allows for the
different affinities and activities of drugs. This allows for more specific drug targeting,
such as targeting the nicotinic receptor in one region of the CNS for hypertension without
affecting other regions of the CNS that could lead to muscle paralysis. A specific example
is Reminyl, anacetylcholinesterase blocker now used for Alzheimer’s disease, in which
recent evidence showed that it increases the activity of nicotinic receptors in the brain
without affecting nicotinic receptors elsewhere in the body. This increase in
pharmacological specificity, allows for the use of drugs with fewer side effects.
3. Discuss the structural difference between the Na-pump and the Na-dependent
glucose transporter.
The Na-pump is a tetramer composed of 2 subunits (22). The consists of 10
trans-membrane -helices and both its N-terminus and C-terminus are intracellular.
There is a large intracellular loop between the 4th and 5thtransmembrane-helices. The
subunit also contains the ATP, Na+, K+ binding sites as well as the phosphorylation site.
The subunit is much smaller and only has one transmembrane domain. It contains a
large extraceullular C-terminus that is glycosylated and a small intracellular N-terminus.
2 and a subunits come together in the membrane and undergo conformational
changes to transport Na+ out and K+ in.
The Na dependent glucose transporter is different in structure in that it consists of
only one large monomeric integral membrane protein consisting of 12 transmembrane-
helical domains. The long protein has both its N-terminus and C-terminus on the
cytoplasmic side and has a large extracullular loop between the 3rd and 4thtransmembrane
domain that is glycosylated.
Document Summary
In the closed state, the kink in the centre of each m2 helix points inward, constricting the passageway. In the absence of ligand (ach for nicotinic and gaba for gaba), the c loop is in an open and uncapped conformation. The pore can now allow the movement of ions to pass through. Distinct allosteric sites exist which allows for the modification of activity and cytoplasmic determinants also control the magnitude of ion flow. 2. 4) discuss the diversity of subunit composition of these channels and the potential significance of this subunit heterogeneity. Heterogeneity refers to the many receptor subtypes of the nicotinic acetylcholine and. The different subtypes and locations of expression allows for the different affinities and activities of drugs. This allows for more specific drug targeting, such as targeting the nicotinic receptor in one region of the cns for hypertension without affecting other regions of the cns that could lead to muscle paralysis.
