part ii structure and catalysis 5 amino acids, peptides, and proteins 6 the three-dimensional...

Part II Structure and Catalysis

5 Amino Acids, Peptides, and Proteins 6 The Three-Dimensional Structure of Proteins 7 Protein Function 8 Enzymes 9 Carbohydrates and Glycobiology10 Nucleotides and Nucleic Acids11 Lipids12 Biological Membranes and Transport13 Biosignaling

Chapter 13 Biosignaling

Molecular Mechanisms of Signal Transduction

Scatchard Plot: Quantifies the Receptor-Ligand Interaction

R + L RL

Four general types of signal transducers

Gated Ion ChannelsIon Channels Underlie Electrical Signaling in Excitable Cells

Transmembrane electrical potential

The Nicotinic Acetylcholine Receptor is a Ligand-Gated Ion Channels

CH3-N-CH2CH2O-C-CH3

CH3

CH3 O+

Voltage-Gated Ion Channels Produce Neuronal Action Potential

Neurons Have Receptor Channels That Respond to A Variety of Neurotransmitters

Glycine, glutamate, serotonin,-aminobutyric acid (GABA)

Receptor Enzymes

Tyrosine-specific proteinkinase

Regulation of gene expression by insulin

Activation of glycogen synthase by insulin

Guanylyl Cyclase is a Receptor Enzyme that Generates The Second Messenger cGMP

Atrial Natriuretic Factor Heart ANF Kidney ANF/ANFR cGMP

Na+/H2O out

(diarrhea)

cGMP-dependent protein kinase PKG

G protein-Coupled Receptors and Second Messengers

Serpentine receptors

-adrenergic receptor

Gs:Stimulatory G protein(, and subunits)

(Adrenaline)

Interaction of Gs with adenylyl cyclase (AC)

AC

Gs

GTP

Forskolin

Self-inactivation of Gs

AC

Activation of cAMP-dependent protein kinase, PKA

a C subunit of PKA

PKI

ATP

Epinephrine Cascade

Degradation of cAMP by Cyclic Nucleotide Phosphodiesterase

Desensitization of the -Adrenergic Receptor

-arrestin

Two Second Messengers Are Derived from Phosphatidylinositols

(IP3)

Diacylglycerol (DG)

Protein kinase C (PKC)

Gq

Phospholipase C

Calcium Is a Second Messenger in Many Signal Transductions

Cytosolic [Ca2+] < 10-7 M

norepinephrine

A single hepatocyteThymocytes (loaded with fura dye)

Calmodulin (CaM)

CaM kinase II peptide

Sensory Transduction in Vision, Olfaction, and Gustation

Light reception in the vertebrate eye

(colors)

(low levels of light)

inner outer segment

(visual cortex of the brain)

Light-induced hyperpolarization of rod cells

(Light induces degradation of cGMP)

Likely structure of rhodopsin complexed with G protein transducin

11-cis-retinal

opsin(rhodopsin)

transducin( subunits)

Molecular consequences of photon absorption by rhodopsin

Cone cells specialize in color vision – different opsins

Color Blindness

red- or green-

dichromats

Vertebrate Olfaction, and Gustation Use Mechanisms Similar to the Visual System

Common features of signaling systems that detects hormones, light, smells, and tetastes

Toxins produced by bacteria that cause cholera and whooping cough (pertussis)

Regulation of Transcription by Steroid Hormons

Antagonist of estrogen- breast cancer treatment

Antagonist of progesterone- terminate early pregnancies

Antagonist of steroid hormones as drugs

Regulation of Cell Cycle by Protein Kinases

Eukaryotic cell cycle

Activation of cyclin-dependent protein kinase (CDKs) by cyclin and phosphorylation

T loop(mask active site)

ATP

CDK2

Cyclin

P-Thr

Glu51

Variation in the activities of specific CDKs during the cell cycle in animals

Regulation of CDK by phosphorylation and proteolysis

DBRP: destruction box recognizing protein

Regulation of cell division by growth factors

Regulation of passage from G1 to S by phosphorylation of pRb

pRb, retinoblastoma protein

Oncogenes, Tumor Suppressor Genes, and Programmed Cell Death

Oncogenes are mutant forms of the genes for protein that regulate the cell cycle

Conversion of a regulatory gene into a viral oncogene

Oncogene-encoded defective EGF receptor

Breast, stomach, and ovary cancers

From Normal Epithelial Cell to Colorectal Cancer

Initial events of apoptosis