molecular cell biology
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Molecular Cell Biology. Professor Dawei Li [email protected] 3420-4744. Textbook: MOLECULAR CELL BIOLOGY 6th Ed Lodish • Berk • Kaiser • Krieger • Scott • Bretscher •Ploegh • Matsudaira. Part 1. Chemical and Molecular Foundations. Life Begins with Cells (p1-30) (Questions) - PowerPoint PPT PresentationTRANSCRIPT
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Molecular Cell BiologyProfessor Dawei Li [email protected] 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
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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
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• 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)
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Figure 3-1
Overview ofprotein structureand function.
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Figure 3-2
Four levels of protein hierarchy.
3.1 Hierarchical Structure of Proteins
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Figure 3-3
Structure of a polypeptide.
The primary Structure of a Protein Is Its LinearArrangement of Amino Acids
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Figure 3-4
The helix,a common secondarystructure in protein.
Secondary Structures Are the Core Elements of Protein Architecture
The Helix
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Figure 3-5The sheet,another common secondary structure in proteins.
β
The Sheetβ
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Figure 3-6 Structure of a turn.β
β Turns
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Figure 3-7 Oil drop model of protein folding.
Overall Folding of a Polypeptide Chain Yields Its Tertiary Structure
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Figure 3-8 Four ways to visualize protein structure.
Different Ways of Depicting the Conformation of Proteins Convey Different Types of Information
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Structural Motifs Are Regular Combinations of Secondary and Tertiary Structures
Figure 3-9 Motifs of protein secondary structure.
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Structural and Functional Domains Are Modules of Tertiary Structure
Figure 3-10 Tertiary and quaternary levels of structure.
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Structural and Functional Domains Are Modules of Tertiary Structure
Figure 3-11 Modular nature of protein domains.
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Protein Associate into Multimeric Structures and Macromolecular Assemblies
Figure 3-12 A macromolecularmachine:the transcription-initiationcomplex.
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Members of Protein Families Have a Common Evolutionary Ancestor
Figure 3-13 Evolution of the globin protein family.
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The 9 Key Concepts of Section 3.1 (p73)
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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.
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Information Directing a Protein's Folding Is Encoded In ItsAmino Acid Sequence
Figure 3-15Hypothetical protein-foldingpathway.
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Molecular Chaperones
Figure 3-16 Chaperone-mediated protein folding.
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Chaperonins
Figure 3-17 Chaperonin-mediated protein folding.
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Alternatively Folded Proteins Are Implicated in Diseases
Figure 3-18 Alzheimer's disease is characterizes by theformation of insoluble plaques composed of amyloid protein.
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The 6 Key Concepts of Section 3.2 (p78)
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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
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Figure 3-19 (b)Protein-ligand binding of anti-bodies.
Specific Binding of Ligands Underlies the Functions of most Proteins
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Enzymes Are Highly Efficient and Specific Catalysts
Figure 3-20 Effect of an enzyme on the activation energy of a chemical reaction.
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An Enzyme's Active Site Binds Substrates and Carries Out Catalysis
Figure 3-21 Active site of the enzyme trypsin.
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An Enzyme's Active Site Binds Substrates and Carries Out Catalysis
Figure 3-22 and for an enzyme-catalyzed reaction.
mK
mK maxV
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An Enzyme's Active Site Binds Substrates and Carries Out Catalysis
Figure 3-22 (a) and for an enzyme-catalyzed reaction.
mK maxV
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An Enzyme's Active Site Binds Substrates and Carries Out Catalysis
Figure 3-22 (b) and for an enzyme-catalyzed reaction.
mK maxV
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An Enzyme's Active Site Binds Substrates and Carries Out Catalysis
Figure 3-23Schematic model of an enzyme's reaction mechanism.
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An Enzyme's Active Site Binds Substrates and Carries Out Catalysis
Figure 3-24 Free-energy reaction profiles of uncatalyzedand multistep enzyme-catalyzed reaction.
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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.
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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
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Serine Proteases Demonstrate How an Enzyme's Active Site Works
Figure 3-25(a)Substrate binding in the active site of typsinlike serine proteases.
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Figure 3-25(b)Substrate binding in the active site of typsinlike serine proteases.
Serine Proteases Demonstrate How an Enzyme's Active Site Works
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Serine Proteases Demonstrate How an Enzyme's Active Site Works
Figure 3-26 Mechanism of serine protease-mediated hydrolysis of peptide bonds.
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This side-chain of His-57 facilitates catalysis by withdrawing and donationg protons throughout the reaction(inset).
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Movements of electrons are indicated by arrows.This attack results in the formation of a transition state called the tetrahedral intermediate
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Additional electron movements result in the breaking of the peptide bond,release of one of the reaction products,and formation of the acylenzyme.
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An xygen from a solvent water molecule then attacks the carbonyl carbon of the acyl enzyme.
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The formation of a second tetrahedral intermediate.
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Additional electron movements result in the breaking of theSer-195-substrate bond and release of the final reaction product.
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Serine Proteases Demonstrate How an Enzyme's Active Site Works
Figure 3-27pH dependence of enzyme activity.
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Enzymes in a Common Pathway Are Often Physically Associated with One Another
Figure 3-28Assembly of enzymes into efficient multi-enzyme complexes.
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Figure 3-28(a)Assembly of enzymes into efficient multi-enzyme complexes.
Enzymes in a Common Pathway Are Often Physically Associated with One Another
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Figure 3-28(b)Assembly of enzymes into efficient multienzyme complexes.
Enzymes in a Common Pathway Are Often Physically Associated with One Another
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Figure 3-28(c)Assembly of enzymes into efficient multienzyme complexes.
Enzymes in a Common Pathway Are Often Physically Associated with One Another
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The 18 Key Concepts of Section 3.3 (p85-86)
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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.
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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.
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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.
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Switching Mediated by Guanine Nucleotide-Binding Proteins
Figure 3-32 The GTPase switch.
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Phosphorylation and Dephosphorylation Covalently Regulate Protein Activity
Figure 3-33 Regulation of protein activityby the kinase/phosphatase switch.
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Coagulation Factor VIII Activation
Regulation III: Proteolytic Cleavage Activates or Inactivates Proteins
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http://virology.biken.osaka-u.ac.jp/English/BDV.html
Protein regulation IV: Sub-cellular location change
Protein P retains p38N to the nuclear
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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