RECEPTORS

The role of the receptor

These are Globular proteins
Located mostly in the cell membrane
Receive messages from chemical messengers coming from other cells (CNS)
Transmit a message into the cell leading to a cellular effect
Different receptors specific for different chemical messengers
Each cell has a range of receptors in the cell membrane making it responsive to different chemical messengers

Neurotransmitters:

Chemicals released from nerve endings which travel across a nerve synapse to bind with receptors on target cells, such as muscle cells or another nerve.
Usually short lived and responsible for messages between individual cells

Hormones:

Chemicals released from cells or glands and which travel some distance to bind with receptors on target cells throughout the body

Note: Chemical messengers ‘switch on’ receptors without undergoing a reaction

Receptors contain a binding site (hollow or cleft on the receptor surface) that is recognised by the chemical messenger
Binding of the messenger involves intermolecular bonds
Binding results in an induced fit of the receptor protein
Change in receptor shape results in a ‘domino’ effect
Domino effect is known as signal transduction, leading to a chemical signal being received inside the cell
Chemical messenger does not enter the cell. It departs the receptor unchanged and is not permanently bound

The Binding Site

A hydrophobic hollow or cleft on the receptor surface – equivalent to the active site of an enzyme
Accepts and binds a chemical messenger
Contains amino acids which bind the messenger
No reaction or catalysis takes place
Binding site is nearly the correct shape for the messenger
Binding alters the shape of the receptor (induced fit)
Altered receptor shape leads to further effects – signal transduction

Induced Fit

Binding interactions must be strong enough to hold the messenger sufficiently long for signal transduction t o take place Interactions must be weak enough to allow the messenger to depart Implies a fine balance Designing molecules with stronger binding interactions results in drugs that block the binding site – antagonists

Main Types of Receptor

ION CHANNEL RECEPTORS
G-PROTEIN-COUPLED RECEPTORS
KINASE-LINKED RECEPTORS
INTRACELLULAR RECEPTORS

Ion Channel Receptors

Receptor protein is part of an ion channel protein complex
Receptor binds a messenger leading to an induced fit
Ion channel is opened or closed
Ion channels are specific for specific ions (Na+, Ca2+, Cl–, K+)
Ions flow across cell membrane down concentration gradient
Polarized or depolarized nerve membranes
Activates or deactivates enzyme catalyzed reactions within cell

Gating

Chemical messenger binds to receptor binding site
Induced fit results in further conformational changes
TM2 segments rotate to open central pore
Fast response measured in msec
Ideal for transmission between nerves
Binding of messenger leads directly to ion flows across cell membrane
Ion flow = secondary effect (signal transduction)
Ion concentration within cell alters
Leads to variation in cell chemistry

G Protein–Coupled Receptors

That Activate or Inhibit Adenylyl Cyclase
the very large group of cell surface receptors that are coupled to signal-transducing trimeric G proteins.
All G protein–coupled receptors (GPCRs) contain seven membrane-spanning regions with their N-terminal segment on the exoplasmic face and their C-terminal segment on the cytosolic face of the plasma membrane .
The GPCR family includes receptors for numerous hormones and neurotransmitters, light activated receptors (rhodopsins) in the eye, and literally thousands of odorant receptors in the mammalian nose.
The signal-transducing G proteins contain three subunits designated α , β, and ϒ. During intracellular signaling the β and ϒ subunits remain bound together and are usually referred to as the Gβϒ subunit. The Gα subunit is a GTPase
switch protein that alternates between an active (on) state with bound GTP and an inactive (off) state with bound GDP.
Stimulation of a coupled receptor causes activation of the G protein, which in turn modulates the activity of an associated effector protein.
Although the effector protein most commonly is activated by Gα ·GTP, in some cases it is inhibited. Moreover, depending on the cell and ligand,
the Gβϒ subunit, rather than Gα·GTP, may transduce the signal to the effector protein.
In addition, the activity of several different effector proteins is controlled by different GPCR-ligand complexes.
All effector proteins, however, are either membrane-bound ion channels or enzymes that catalyze formation of second messengers (e.g., cAMP, DAG, and IP3).
These variations on the theme of GPCR signaling arise because multiple G proteins are encoded in eukaryotic genomes.
The human genome, for example, encodes 27 different Gα, 5 Gβ, and 13 Gϒ subunits. So far as is known, the different Gβϒ subunits function similarly.

Bacteriorhodopsin & Rhodopsin Family

Rhodopsin = visual receptor
Many common receptors belong to this same family
Implications for drug selectivity depending on similarity (evolution)
Membrane bound receptors difficult to crystallize
X-Ray structure of bacteriorhodopsin solved – bacterial protein similar to rhodopsin
Bacteriorhodopsin structure used as ‘template’ for other receptors
Construct model receptors based on template and amino acid sequence
Leads to model binding sites for drug design
Crystal structures for rhodopsin and b2-adrenergic receptors now solved – better templates

Tyrosine kinase – linked receptors

Bifunctional receptor / enzyme
Activated by hormones
Protein serves a dual role – receptor plus enzyme
The receptor binds messenger leading to an induced fit
Protein changes shape and opens active site
The reaction catalyzed within cell
Overexpression related to several cancers

Epidermal growth factor receptor (EGF- R)

Active site on one half of dimer catalyzes phosphorylation of Tyr residues on other half
Dimerisation of receptor is crucial
Phosphorylated regions act as binding sites for further proteins and enzymes
Results in activation of signaling proteins and enzymes
Message carried into cell

Intracellular receptors

Chemical messengers must cross the cell membrane
Chemical messengers must be hydrophobic
Example-steroids and steroid receptors

Cyclic ADP-ribose (cADPR),

The receptor (which may be composed of four subunits) leads to the opening of Ca2+ channels and an influx of Ca2+ in to the cytoplasm from the vacuole and the ER

ETR1 –ETHYLENE RECEPTOR 1

The ethylene(G) regulates ripening, germination, elongation, senescence, and pathogen responses.
ETR1, a 79-kDa protein
ETR1 exists as a dimer in the plasma membrane.
Ethylene joins the two monomers together and permits intermolecular phosphorylation.
Mutations in ETR1 (designated efr1) lead to loss of physiological sensitivity to ethylene.

Auxin-binding protein (ABP1)

IAA
Growth regulator
Functions in cell division and expansion.

Phytochrome

Phytochrome is a photoreceptor, a pigment that plants and some bacteria and fungi use to detect light.
It is sensitive to light in the red and far -red region of the visible spectrum
In other word a blue green pigment found in many plant in which it regulates various development processes.
The long day plant is flower after short exposure to red light the red light is absorbed by phytochrome 660 nm which converts to P730 nm and induces flowering.
Short day plants absorb light p730 which is converted to p660nm. This is a much slover and needs a long dark period.

1. What is the primary role of receptors in cells?

A) To catalyze chemical reactions
B) To receive and transmit messages from chemical messengers
C) To break down neurotransmitters
D) To transport ions across membranes

✅ Answer: B) To receive and transmit messages from chemical messengers

2. Where are most receptors located?

A) Inside the cytoplasm
B) Embedded in the mitochondria
C) Mostly on the cell membrane
D) Inside the nucleus

✅ Answer: C) Mostly on the cell membrane

3. Neurotransmitters differ from hormones because they:

A) Travel longer distances in the body
B) Are always produced by glands
C) Are usually short-lived and act between individual cells
D) Do not interact with receptors

✅ Answer: C) Are usually short-lived and act between individual cells

4. What happens to a receptor when a chemical messenger binds to it?

A) The receptor gets permanently attached to the messenger
B) The receptor undergoes an induced fit and changes shape
C) The receptor gets destroyed
D) The receptor starts producing ATP

✅ Answer: B) The receptor undergoes an induced fit and changes shape

5. Which of the following is NOT a major type of receptor?

A) Ion Channel Receptors
B) G-Protein-Coupled Receptors
C) Ribosome-Linked Receptors
D) Kinase-Linked Receptors

✅ Answer: C) Ribosome-Linked Receptors

6. How do ion channel receptors function?

A) They break down neurotransmitters
B) They open or close an ion channel when a messenger binds
C) They transport hormones into the cell
D) They act as enzymes to catalyze reactions

✅ Answer: B) They open or close an ion channel when a messenger binds

7. What does GPCR stand for?

A) Gene-Protein Complex Regulator
B) Gated Protein Carrier Receptor
C) G-Protein-Coupled Receptor
D) General Protein-Control Receptor

✅ Answer: C) G-Protein-Coupled Receptor

8. What is the function of the Gα subunit in GPCR signaling?

A) It binds to neurotransmitters
B) It acts as a switch protein by alternating between active (GTP) and inactive (GDP) states
C) It transports ions across membranes
D) It degrades hormones

✅ Answer: B) It acts as a switch protein by alternating between active (GTP) and inactive (GDP) states

9. Which second messengers are commonly involved in GPCR signaling?

A) ATP and NADPH
B) cAMP, DAG, and IP3
C) Glucose and lipids
D) Water and CO₂

✅ Answer: B) cAMP, DAG, and IP3

10. What is the main function of tyrosine kinase-linked receptors?

A) Transport of small molecules across membranes
B) Activation of signal transduction pathways by phosphorylation
C) Breakdown of neurotransmitters
D) Passive diffusion of hormones

✅ Answer: B) Activation of signal transduction pathways by phosphorylation

11. Which receptor is responsible for detecting light in the human eye?

A) Phytochrome
B) Rhodopsin
C) Ethylene Receptor
D) Auxin-Binding Protein

✅ Answer: B) Rhodopsin

12. Why is the bacteriorhodopsin structure important for drug design?

A) It helps in studying bacterial infections
B) It is similar to human rhodopsin and serves as a model for other receptors
C) It directly breaks down drugs
D) It binds to neurotransmitters

✅ Answer: B) It is similar to human rhodopsin and serves as a model for other receptors

13. Overexpression of tyrosine kinase-linked receptors is associated with:

A) Muscle contraction
B) Several cancers
C) Increased neurotransmitter breakdown
D) ATP synthesis

✅ Answer: B) Several cancers

14. Which receptor is involved in regulating plant growth and elongation?

A) Rhodopsin
B) ETR1
C) Auxin-Binding Protein (ABP1)
D) Tyrosine Kinase Receptor

✅ Answer: C) Auxin-Binding Protein (ABP1)

15. Which plant photoreceptor regulates flowering based on light exposure?

A) ETR1
B) Rhodopsin
C) Phytochrome
D) GPCR

✅ Answer: C) Phytochrome

16. What is the function of ETR1 in plants?

A) Controls muscle contraction
B) Detects neurotransmitters
C) Regulates ethylene response and plant growth processes
D) Functions in glucose metabolism

✅ Answer: C) Regulates ethylene response and plant growth processes

17. What happens when ETR1 is mutated?

A) Increased response to light
B) Loss of sensitivity to ethylene
C) Uncontrolled plant growth
D) Increased ATP synthesis

✅ Answer: B) Loss of sensitivity to ethylene

18. Which molecule functions as a growth regulator by affecting cell division and expansion?

A) Rhodopsin
B) Phytochrome
C) Auxin-Binding Protein (ABP1)
D) cAMP

✅ Answer: C) Auxin-Binding Protein (ABP1)

19. What happens when phytochrome absorbs red light at 660 nm?

A) It breaks down
B) It converts into P730 and induces flowering in long-day plants
C) It gets inactivated
D) It stops ATP production

✅ Answer: B) It converts into P730 and induces flowering in long-day plants

20. Which receptor allows the release of Ca²⁺ from the ER into the cytoplasm?

A) GPCR
B) Tyrosine Kinase Receptor
C) Cyclic ADP-Ribose (cADPR) Receptor
D) ETR1

✅ Answer: C) Cyclic ADP-Ribose (cADPR) Receptor

21. What is the primary function of receptors in signal transduction?

A) To permanently bind chemical messengers
B) To break down neurotransmitters
C) To receive chemical signals and trigger a cellular response
D) To transport ions directly into the nucleus

✅ Answer: C) To receive chemical signals and trigger a cellular response

22. What type of molecules typically bind to intracellular receptors?

A) Hydrophilic molecules
B) Hydrophobic molecules
C) Only ions
D) Large protein molecules

✅ Answer: B) Hydrophobic molecules

23. Which of the following receptors is an example of an intracellular receptor?

A) Ion Channel Receptors
B) G-Protein-Coupled Receptors
C) Steroid Hormone Receptors
D) Kinase-Linked Receptors

✅ Answer: C) Steroid Hormone Receptors

24. Which second messenger is produced when adenylyl cyclase is activated?

A) cAMP
B) ATP
C) NADH
D) GTP

✅ Answer: A) cAMP

25. In a G-protein-coupled receptor, what happens when GDP is replaced by GTP on the Gα subunit?

A) The receptor gets permanently deactivated
B) The G protein is activated and transmits a signal
C) The G protein breaks down the chemical messenger
D) The receptor undergoes degradation

✅ Answer: B) The G protein is activated and transmits a signal

26. What happens to the chemical messenger after it binds to a receptor?

A) It enters the cell and gets used as energy
B) It undergoes a chemical reaction
C) It departs the receptor unchanged after signal transduction
D) It gets permanently stuck to the receptor

✅ Answer: C) It departs the receptor unchanged after signal transduction

27. What does the term “induced fit” mean in receptor binding?

A) The receptor destroys the messenger upon binding
B) The receptor undergoes a shape change after binding to the messenger
C) The messenger permanently changes the receptor
D) The receptor and messenger undergo a chemical reaction

✅ Answer: B) The receptor undergoes a shape change after binding to the messenger

28. Which receptor type directly regulates ion flow across the membrane?

A) Kinase-linked receptors
B) Ion Channel Receptors
C) G-Protein-Coupled Receptors
D) Intracellular Receptors

✅ Answer: B) Ion Channel Receptors

29. What is the function of the β and γ subunits in GPCR signaling?

A) They remain bound together and can transduce signals in some cases
B) They break down the neurotransmitter
C) They form an ion channel
D) They convert ATP into ADP

✅ Answer: A) They remain bound together and can transduce signals in some cases

30. What is the role of phosphodiesterase in GPCR signaling?

A) It synthesizes cAMP
B) It breaks down cAMP to terminate the signal
C) It activates ion channels
D) It inhibits enzyme activity

✅ Answer: B) It breaks down cAMP to terminate the signal

31. What is the primary function of kinase-linked receptors?

A) To directly open ion channels
B) To activate intracellular enzymes through phosphorylation
C) To release neurotransmitters
D) To transport small molecules across membranes

✅ Answer: B) To activate intracellular enzymes through phosphorylation

32. What is a key feature of epidermal growth factor receptor (EGF-R) activation?

A) It breaks down ATP
B) It functions as an ion channel
C) It requires dimerization and phosphorylation
D) It binds to neurotransmitters

✅ Answer: C) It requires dimerization and phosphorylation

33. What role do phosphorylation sites on kinase receptors play?

A) They act as binding sites for signaling proteins
B) They break down ATP
C) They block ion transport
D) They degrade chemical messengers

✅ Answer: A) They act as binding sites for signaling proteins

34. What kind of receptor does ethylene bind to in plants?

A) Rhodopsin
B) G-Protein-Coupled Receptor
C) ETR1 (Ethylene Receptor)
D) Auxin-Binding Protein

✅ Answer: C) ETR1 (Ethylene Receptor)

35. What happens when ETR1 is mutated?

A) The plant becomes more sensitive to ethylene
B) The plant loses sensitivity to ethylene
C) The plant stops growing
D) The plant produces more neurotransmitters

✅ Answer: B) The plant loses sensitivity to ethylene

36. What is the main function of auxin-binding protein (ABP1)?

A) To regulate ethylene production
B) To detect light
C) To regulate plant growth by affecting cell division and expansion
D) To facilitate ATP production

✅ Answer: C) To regulate plant growth by affecting cell division and expansion

37. What is the function of cyclic ADP-ribose (cADPR) receptors?

A) To regulate neurotransmitter release
B) To open Ca²⁺ channels and allow calcium influx
C) To detect light in plants
D) To control glucose metabolism

✅ Answer: B) To open Ca²⁺ channels and allow calcium influx

38. Phytochrome is a photoreceptor sensitive to which type of light?

A) Infrared and ultraviolet
B) Blue and green
C) Red and far-red
D) Yellow and orange

✅ Answer: C) Red and far-red

39. How does phytochrome regulate flowering in long-day plants?

A) It absorbs red light (660 nm) and converts into P730, which induces flowering
B) It absorbs blue light and triggers ATP production
C) It converts P730 into P660, leading to flowering
D) It blocks the action of ethylene

✅ Answer: A) It absorbs red light (660 nm) and converts into P730, which induces flowering

40. In short-day plants, what happens to phytochrome during long dark periods?

A) P730 gets converted to P660, preventing flowering
B) P660 gets converted to P730, triggering flowering
C) Phytochrome breaks down completely
D) Phytochrome stops responding to light

✅ Answer: A) P730 gets converted to P660, preventing flowering