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Lecture Notes for Chapter 10 Signaling PowerPoint PPT Presentation


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Essential Biochemistry Third Edition Charlotte W. Pratt | Kathleen Cornely. Lecture Notes for Chapter 10 Signaling. KEY CONCEPTS: Section 10-1. Receptor-ligand binding is described in terms of a dissociation constant.

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Lecture Notes for Chapter 10 Signaling

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Lecture notes for chapter 10 signaling

Essential Biochemistry

Third Edition

Charlotte W. Pratt | Kathleen Cornely

Lecture Notes for

Chapter 10

Signaling


Key concepts section 10 1

KEY CONCEPTS: Section 10-1

  • Receptor-ligand binding is described in terms of a dissociation constant.

  • G protein-coupled receptors and receptor tyrosine kinases are the two major types of receptors that transduce extracellular signals to the cell interior.

  • Regulatory mechanisms limit the extent of signaling.


Extracellular signals can take on many forms

Extracellular signals can take on many forms.


A ligand binds to a receptor with a characteristic affinity k d

A ligand binds to a receptor with a characteristic affinity (Kd).

Units:Molarity

  • Kd = [Ligand] when the receptor is half-saturated.

  • Low values of Kd indicate strong binding (high affinity).


Receptor ligand binding is hyperbolic

Receptor-ligand binding is hyperbolic.


A ligand that binds to a receptor and elicits a biological effect is an agonist

A ligand that binds to a receptor and elicits a biological effect is an agonist.

Antagonist of Adenosine Receptor – Caffeine binds but does NOT elicit a response

Natural agonist for Adenosine Receptor


Most signaling occurs through two types of receptors

Most signaling occurs through two types of receptors.

  • G proteins

  • Kinases


Most signaling occurs through two types of receptors1

Most signaling occurs through two types of receptors.

  • G proteins

  • Kinases


Key concepts section 10 2

KEY CONCEPTS: Section 10-2

  • Ligand binding to a G protein-coupled receptor alters its conformation so that an intracellular G protein becomes activated.

  • The G protein stimulates adenylatecyclase to produce the second messenger cAMP, which activates protein kinase A.

  • G protein-dependent signaling is limited by several mechanisms.

  • The phosphoinositide signaling system activates a G protein, which leads to the production of lipid-derived second messengers and the activation of protein kinase C.

  • Cross-talk results when signaling pathways share components.


G protein receptors contain seven transmembrane helices

G protein receptors contain seven transmembrane helices.

Physiological ligands for the β-adrenergic receptor


Gpcrs bind to and activate a g protein

GPCRs bind to and activate a G protein.

Complex

Receptor

G Protein

G Protein with GDP (orange) bound


The g protein cycle

The G Protein Cycle

Signaling is limited by the GTPase activity of the α subunit


A major target of activated g protein is adenylate cyclase

A major target of activated G protein is adenylate cyclase.


Camp activates protein kinase a

cAMP activates Protein Kinase A.

PKA

R = Regulatory subunit

C = Catalytic subunit

  • The level of cAMP determines the level of activity of PKA.


The structure of protein kinase a

The Structure of Protein Kinase A

Zoomed in view of active site


Signaling pathways are also switched off

Signaling pathways are also switched off.


Arrestin reduces a gpcr s ability to activate a g protein

Arrestin reduces a GPCR’s ability to activate a G protein.


The phosphoinositide signaling pathway generates two second messengers

The phosphoinositide signaling pathway generates two second messengers.


Calmodulin mediates some ca 2 signals

Calmodulin mediates some Ca2+ signals.

Ca2+

Calmodulin has an extended shape.

Calmodulin wraps around

its protein target!


Key concepts section 10 3

KEY CONCEPTS: Section 10-3

  • Ligands such as insulin activate the tyrosine kinase activity of their receptors.

  • Receptor tyrosine kinases trigger cellular responses by phosphorylating target proteins and by activating Ras.


The insulin receptor has two ligand binding sites

The insulin receptor has two ligand-binding sites.


Insulin receptor tyrosine kinase undergoes autophosphorylation

Insulin receptor tyrosine kinase undergoes autophosphorylation.

Light blue = inactive receptor

Dark blue = activation loop

Light green = active receptor

Dark green = activation loop

  • A conformational change occurs to facilitate autophosphorylation.


Ras is active as long as gtp is bound to it

Ras is active as long as GTP is bound to it.


Key concepts section 10 4

KEY CONCEPTS: Section 10-4

  • Lipid hormones bind to intracellular receptors that regulate gene expression.

  • Eicosanoids are local mediators that act through G protein-coupled receptors.


Some hormones are lipids that do not bind to receptors

Some hormones are lipids that do not bind to receptors.


Some receptors are transcription factors

Some receptors are transcription factors.

The Glucocorticoid Receptor-DNA Complex


Arachidonate gets converted to eicosanoid signaling molecules

Arachidonate gets converted to eicosanoid signaling molecules.


Aspirin inhibits cyclooxygenase

Aspirin inhibits cyclooxygenase.

  • Prostaglandin synthesis is inhibited, thereby reducing pain.


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