Molecular Cell BiologyProfessor Dawei Li daweili@sjtu.edu.cn 3420-4744

1. Life Begins with Cells (p1-30) (Questions)

2. Chemical Foundations (p31-62) (Self-review) (1Characteristics of amino acids, 2 Interacting forces)

3. Protein Structure and Function (p63-110) (Selected Contents)

Part 1. Chemical and Molecular Foundations

Textbook: MOLECULAR CELL BIOLOGY 6th EdLodish • Berk • Kaiser • Krieger • Scott • Bretscher •Ploegh • Matsudaira

1. Life Begins with Cells (p1-30) Q&A

2. Chemical Foundations (p31-62) (Self-review) 1. Characteristics of amino acids:

2. Interacting forces:

Review

• 3.1 Hierarchical Structure of Proteins

• 3.2 Protein Folding

• 3.3 Protein Function

• 3.4 Regulating Protein Function I:

Protein Degradation

• 3.5 Regulating Protein Function II

Noncovalent and Covalent Modifications

• 3.6 Purifying, Detecting, and Characterizing Proteins

• 3.7 Proteomics

Chapter 3 Protein Structure and Function (63-110)

Figure 3-1

Overview ofprotein structureand function.

Figure 3-2

Four levels of protein hierarchy.

3.1 Hierarchical Structure of Proteins

Figure 3-3

Structure of a polypeptide.

The primary Structure of a Protein Is Its LinearArrangement of Amino Acids

Figure 3-4

The helix,a common secondarystructure in protein.

Secondary Structures Are the Core Elements of Protein Architecture

The Helix

Figure 3-5The sheet,another common secondary structure in proteins.

β

The Sheetβ

Figure 3-6 Structure of a turn.β

β Turns

Figure 3-7 Oil drop model of protein folding.

Overall Folding of a Polypeptide Chain Yields Its Tertiary Structure

Figure 3-8 Four ways to visualize protein structure.

Different Ways of Depicting the Conformation of Proteins Convey Different Types of Information

Structural Motifs Are Regular Combinations of Secondary and Tertiary Structures

Figure 3-9 Motifs of protein secondary structure.

Structural and Functional Domains Are Modules of Tertiary Structure

Figure 3-10 Tertiary and quaternary levels of structure.

Structural and Functional Domains Are Modules of Tertiary Structure

Figure 3-11 Modular nature of protein domains.

Protein Associate into Multimeric Structures and Macromolecular Assemblies

Figure 3-12 A macromolecularmachine:the transcription-initiationcomplex.

Members of Protein Families Have a Common Evolutionary Ancestor

Figure 3-13 Evolution of the globin protein family.

The 9 Key Concepts of Section 3.1 (p73)

3.2 Protein Folding

Planar Peptide Bonds Limit the Shapes into which Proteins Can Fold

Figure 3-14 Rotation between planar peptide groups in proteins.

Information Directing a Protein's Folding Is Encoded In ItsAmino Acid Sequence

Figure 3-15Hypothetical protein-foldingpathway.

Molecular Chaperones

Figure 3-16 Chaperone-mediated protein folding.

Chaperonins

Figure 3-17 Chaperonin-mediated protein folding.

Alternatively Folded Proteins Are Implicated in Diseases

Figure 3-18 Alzheimer's disease is characterizes by theformation of insoluble plaques composed of amyloid protein.

The 6 Key Concepts of Section 3.2 (p78)

3.3 Protein FunctionSpecific Binding of Ligands Underlies the Functions of most Proteins

Figure 3-19 (a)Protein-ligand binding of anti-bodies.

CDR: Complemetarity-Determining Region

Figure 3-19 (b)Protein-ligand binding of anti-bodies.

Specific Binding of Ligands Underlies the Functions of most Proteins

Enzymes Are Highly Efficient and Specific Catalysts

Figure 3-20 Effect of an enzyme on the activation energy of a chemical reaction.

An Enzyme's Active Site Binds Substrates and Carries Out Catalysis

Figure 3-21 Active site of the enzyme trypsin.

An Enzyme's Active Site Binds Substrates and Carries Out Catalysis

Figure 3-22 and for an enzyme-catalyzed reaction.

mK

mK maxV

An Enzyme's Active Site Binds Substrates and Carries Out Catalysis

Figure 3-22 (a) and for an enzyme-catalyzed reaction.

mK maxV

An Enzyme's Active Site Binds Substrates and Carries Out Catalysis

Figure 3-22 (b) and for an enzyme-catalyzed reaction.

mK maxV

An Enzyme's Active Site Binds Substrates and Carries Out Catalysis

Figure 3-23Schematic model of an enzyme's reaction mechanism.

An Enzyme's Active Site Binds Substrates and Carries Out Catalysis

Figure 3-24 Free-energy reaction profiles of uncatalyzedand multistep enzyme-catalyzed reaction.

An Enzyme's Active Site Binds Substrates and Carries Out Catalysis

Figure 3-24(a) Free-energy reaction profiles of uncatalyzedand multistep enzyme-catalyzed reaction.

Figure 3-24(b) Free-energy reaction profiles of uncatalyzedand multistep enzyme-catalyzed reaction.

An Enzyme's Active Site Binds Substrates and Carries Out Catalysis

Serine Proteases Demonstrate How an Enzyme's Active Site Works

Figure 3-25(a)Substrate binding in the active site of typsinlike serine proteases.

Figure 3-25(b)Substrate binding in the active site of typsinlike serine proteases.

Serine Proteases Demonstrate How an Enzyme's Active Site Works

Serine Proteases Demonstrate How an Enzyme's Active Site Works

Figure 3-26 Mechanism of serine protease-mediated hydrolysis of peptide bonds.

This side-chain of His-57 facilitates catalysis by withdrawing and donationg protons throughout the reaction(inset).

Movements of electrons are indicated by arrows.This attack results in the formation of a transition state called the tetrahedral intermediate

Additional electron movements result in the breaking of the peptide bond,release of one of the reaction products,and formation of the acylenzyme.

An xygen from a solvent water molecule then attacks the carbonyl carbon of the acyl enzyme.

The formation of a second tetrahedral intermediate.

Additional electron movements result in the breaking of theSer-195-substrate bond and release of the final reaction product.

Serine Proteases Demonstrate How an Enzyme's Active Site Works

Figure 3-27pH dependence of enzyme activity.

Enzymes in a Common Pathway Are Often Physically Associated with One Another

Figure 3-28Assembly of enzymes into efficient multi-enzyme complexes.

Figure 3-28(a)Assembly of enzymes into efficient multi-enzyme complexes.

Enzymes in a Common Pathway Are Often Physically Associated with One Another

Figure 3-28(b)Assembly of enzymes into efficient multienzyme complexes.

Enzymes in a Common Pathway Are Often Physically Associated with One Another

Figure 3-28(c)Assembly of enzymes into efficient multienzyme complexes.

Enzymes in a Common Pathway Are Often Physically Associated with One Another

The 18 Key Concepts of Section 3.3 (p85-86)

3.4 Regulating Protein Function I:Protein Degradation

The Proteasome Is a ComplexMolecular Machine Used to Degrade Proteins

Figure 3-29 Ubiquitin-and-proteasome-mediated prot-eolysis.

3.5 Regulating Protein Function II:Noncovalent and Covalent Modifications

Nonconvalent Binding Permits Allosteric,or Cooperative,Regulation of Proteins

Experimental Figure 3-30Hemoglobin binds oxygen cooperatively.

Nonconvalent Binding of Calcium and GTP Are Widely Used As Allosteric Switches to Control Protein Activity

Ca2+/Calmodulin-Mediated Switching

Figure 3-31 Conformational changes induced by Ca2+ binding to calmodulin.

Switching Mediated by Guanine Nucleotide-Binding Proteins

Figure 3-32 The GTPase switch.

Phosphorylation and Dephosphorylation Covalently Regulate Protein Activity

Figure 3-33 Regulation of protein activityby the kinase/phosphatase switch.

Coagulation Factor VIII Activation

Regulation III: Proteolytic Cleavage Activates or Inactivates Proteins

http://virology.biken.osaka-u.ac.jp/English/BDV.html

Protein regulation IV: Sub-cellular location change

Protein P retains p38N to the nuclear

The 4 Key Concepts of Section 3.4 (p88)

Questions and Answers

Preview Section 3.4-3.7 Figures

Student solution book: select to answer 1 question from P3

Next Class Quiz: one question you prepared