chapter 4
TRANSCRIPT
Chapter 4 Lecture OutlinesProtein Structure and Function
EssentialCell Biology
Third Edition
Copyright © Garland Science 2010
CHAPTER CONTENTSTHE SHAPE AND STRUCTURE OF
PROTEINSHOW PROTEINS WORKHOW PROTEINS ARE CONTROLLEDHOW PROTEINS ARE STUDIED
THE SHAPE AND STRUCTURE OF PROTEINS
• The Shape of a Protein Is Specified by Its Amino Acid Sequence
• Proteins Fold into a Conformation of Lowest Energy• Proteins Come in a Wide Variety of Complicated Shapes• The Alpha Helix and the Beta Sheet Are Common Folding
Patterns• Helices Form Readily in Biological Structures • Beta Sheets Form Rigid Structures at the Core of Many
Proteins• Proteins Have Several Levels of Organization• Few of the Many Possible Polypeptide Chains Will Be
Useful• Proteins Can Be Classified into Families• Large Protein Molecules Often Contain More Than One
Polypeptide Chain• Proteins Can Assemble into Filaments, Sheets, or Spheres• Some Types of Proteins Have Elongated Fibrous Shapes• Extracellular Proteins Are Often Stabilized by Covalent
Cross-Linkages
1 4 7 10 13 16 19ATG GGA GCT CTA TTA ACC TAA met gly ala leu leu thr stop
ATG GGA GCC CTA TTT ACC TAA met gly ala leu phe thr stop
ATG GGA GCC CTA TGA ACC TAA met gly ala leu stop
ATG GGA GCT CTA TTA CAC CTA A met gly ala leu leu his leu
Sequence Change vs Mutation Type
Why/How do mutations cause disease?
Missense Mutation
Nonsense Mutation
Frameshift mutation!!!(insertion/deletion)
Figure 7-25 Essential Cell Biology (© Garland Science 2010)
The code is redundant, some aminoacids are specified by more than one triplet
Different reading frames
Genetic Code
Figure 4-1 Essential Cell Biology (© Garland Science 2010)
The Shape of a Protein Is Specified by Its Amino Acid Sequence
Figure 4-2 Essential Cell Biology (© Garland Science 2010)
The Shape of a Protein Is Specified by Its Amino Acid Sequence
Side chain gives unique properties
Figure 4-3 Essential Cell Biology (© Garland Science 2010)
The Shape of a Protein Is Specified by Its Amino Acid Sequence
Figure 4-4 Essential Cell Biology (© Garland Science 2010)
The Shape of a Protein Is Specified by Its Amino Acid Sequence
noncovalent bonds shape the polypeptide chain
Noncovalent bonds:
Electrostatic attractions
Hydrogen bond
Van der Waals atractions
(Peptide bond is covalent bond)
Figure 4-5 Essential Cell Biology (© Garland Science 2010)
The Shape of a Protein Is Specified by Its Amino Acid Sequence
Hydrohpobic – hydrophilic interactions
Nonpolar - Hydrophobic aa – (phe, leu, val, trp) tend to cluster inside in folded protein(hydrophobic oil droplets coalesce to form larger one)
Polar-Hydrophilic aa – (arg, glu, his) tend to arrange near outside of protein to form H bond with water or other polar molecules
THE SHAPE AND STRUCTURE OF PROTEINS
• The Shape of a Protein Is Specified by Its Amino Acid Sequence
• Proteins Fold into a Conformation of Lowest Energy• Proteins Come in a Wide Variety of Complicated Shapes• The Alpha Helix and the Beta Sheet Are Common Folding
Patterns• Helices Form Readily in Biological Structures • Beta Sheets Form Rigid Structures at the Core of Many
Proteins• Proteins Have Several Levels of Organization• Few of the Many Possible Polypeptide Chains Will Be
Useful• Proteins Can Be Classified into Families• Large Protein Molecules Often Contain More Than One
Polypeptide Chain• Proteins Can Assemble into Filaments, Sheets, or Spheres• Some Types of Proteins Have Elongated Fibrous Shapes• Extracellular Proteins Are Often Stabilized by Covalent
Cross-Linkages
Figure 4-7 Essential Cell Biology (© Garland Science 2010)
Proteins Fold into a Conformation of Lowest Energy
Protein shape is formed to minimize free energy (G)(by spontaneous or molecular chaperons in cytoplasm)
if a protein denatured to destroy folding, it will regain its shape again
Each protein is folded into one stable conformationSometimes the shape of proteins changes by modification or interaction
Modification: methylation, acetylation, phosphorylation of histones
Figure 4-8 Essential Cell Biology (© Garland Science 2010)
Proteins Fold into a Conformation of Lowest Energy
The proper structure of protein is important for its function and solubilityimproper folded protein aggregate in cell, destroy cell (Alzheimer’s disease)
Mis-folded Prion protein aggregates: mad cow disease
Misfolded prion can convert the properly folded prion into misfolded
THE SHAPE AND STRUCTURE OF PROTEINS
• The Shape of a Protein Is Specified by Its Amino Acid Sequence
• Proteins Fold into a Conformation of Lowest Energy• Proteins Come in a Wide Variety of Complicated Shapes• The Alpha Helix and the Beta Sheet Are Common Folding
Patterns• Helices Form Readily in Biological Structures • Beta Sheets Form Rigid Structures at the Core of Many
Proteins• Proteins Have Several Levels of Organization• Few of the Many Possible Polypeptide Chains Will Be
Useful• Proteins Can Be Classified into Families• Large Protein Molecules Often Contain More Than One
Polypeptide Chain• Proteins Can Assemble into Filaments, Sheets, or Spheres• Some Types of Proteins Have Elongated Fibrous Shapes• Extracellular Proteins Are Often Stabilized by Covalent
Cross-Linkages
Figure 4-9 Essential Cell Biology (© Garland Science 2010)
Proteins Come in a Wide Variety of Complicated Shapes
Different shapes different aa sequence, different interactions
Globular or fibrous shape
Different size30 aa to 10000 aa
THE SHAPE AND STRUCTURE OF PROTEINS
• The Shape of a Protein Is Specified by Its Amino Acid Sequence
• Proteins Fold into a Conformation of Lowest Energy• Proteins Come in a Wide Variety of Complicated Shapes• The Alpha Helix and the Beta Sheet Are Common Folding
Patterns• Helices Form Readily in Biological Structures • Beta Sheets Form Rigid Structures at the Core of Many
Proteins• Proteins Have Several Levels of Organization• Few of the Many Possible Polypeptide Chains Will Be
Useful• Proteins Can Be Classified into Families• Large Protein Molecules Often Contain More Than One
Polypeptide Chain• Proteins Can Assemble into Filaments, Sheets, or Spheres• Some Types of Proteins Have Elongated Fibrous Shapes• Extracellular Proteins Are Often Stabilized by Covalent
Cross-Linkages
Figure 4-10 Essential Cell Biology (© Garland Science 2010)
The Alpha Helix and the Beta Sheet Are Common Folding Patterns
Two common folding pattern : alpha helix, beta sheet
These structure formed by H bonding between
N-H and C=O atoms in polypeptide backbone
Figure 4-10a–c Essential Cell Biology (© Garland Science 2010)
α- helix
H-bond between every fourth aminoacid
Abundant in proteins located in cell membrane (transport protein, receptor)
Figure 4-12 Essential Cell Biology (© Garland Science 2010)
α- helix
α- helix crossing lipid bilayerİn membrane
Coiled-coil structure
2 or more α- helix wrap around one another
Rod-like strong fiberkeratin, reinforce layer of skinMyosin, responsible for muscle contraction
Figure 4-10d–f Essential Cell Biology (© Garland Science 2010)
Beta Sheets Form Rigid Structures at the Core of Many Proteins
Beta sheets: H bond between polypeptide chain lying side by side
Antiparallel
parallel
Figure 4-15 Essential Cell Biology (© Garland Science 2010)
Beta Sheets Form Rigid Structures at the Core of Many Proteins
Beta sheets produce very rigid, pleated structure
Silk: extraordinary tensile strengthAntifreeze proteins prevent ice formation in cell
THE SHAPE AND STRUCTURE OF PROTEINS
• The Shape of a Protein Is Specified by Its Amino Acid Sequence
• Proteins Fold into a Conformation of Lowest Energy• Proteins Come in a Wide Variety of Complicated Shapes• The Alpha Helix and the Beta Sheet Are Common Folding
Patterns• Helices Form Readily in Biological Structures • Beta Sheets Form Rigid Structures at the Core of Many
Proteins• Proteins Have Several Levels of Organization• Few of the Many Possible Polypeptide Chains Will Be
Useful• Proteins Can Be Classified into Families• Large Protein Molecules Often Contain More Than One
Polypeptide Chain• Proteins Can Assemble into Filaments, Sheets, or Spheres• Some Types of Proteins Have Elongated Fibrous Shapes• Extracellular Proteins Are Often Stabilized by Covalent
Cross-Linkages
Figure 4-16 Essential Cell Biology (© Garland Science 2010)
Proteins Have Several Levels of Organization
Primary structure: aminoacid sequence, long polypeptide chain
Secondary structure: alpha helix, beta sheet
Tertiary structure: 3-dimentional structure combination of alpha helix, beta sheet
Quaternary structure: protein contain more than one polypeptide chain
GFP
RFPGFP
Change the aminoacids to improve the starch synthesis!
Figure 4-17 Essential Cell Biology (© Garland Science 2010)
Proteins Have Several Levels of Organization
Proteins: long peptide chain
Parts of this long chain called protein domain, specific function
DNA binding domain
Protein-protein interaction domain
Catalytic domain
Transmembrane domain
Figure 4-18 Essential Cell Biology (© Garland Science 2010)
Proteins Can Be Classified into Families
Protein families: proteins share similar features and structures
Polymerases
Proteases (protein cleaving enzyme, digestive function)
Kinases (add P-grup to proteins)
Membrane protein, transcription factors
Two members of proteaseSlight difference- different substrate
THE SHAPE AND STRUCTURE OF PROTEINS
• The Shape of a Protein Is Specified by Its Amino Acid Sequence
• Proteins Fold into a Conformation of Lowest Energy• Proteins Come in a Wide Variety of Complicated Shapes• The Alpha Helix and the Beta Sheet Are Common Folding
Patterns• Helices Form Readily in Biological Structures • Beta Sheets Form Rigid Structures at the Core of Many
Proteins• Proteins Have Several Levels of Organization• Few of the Many Possible Polypeptide Chains Will Be
Useful• Proteins Can Be Classified into Families• Large Protein Molecules Often Contain More Than One
Polypeptide Chain• Proteins Can Assemble into Filaments, Sheets, or Spheres• Some Types of Proteins Have Elongated Fibrous Shapes• Extracellular Proteins Are Often Stabilized by Covalent
Cross-Linkages
Figure 4-19 Essential Cell Biology (© Garland Science 2010)
Large Protein Molecules Often Contain More Than One Polypeptide Chain
Different polypeptide bind each other with weak noncovalent bonds(subunits)
Figure 4-21 Essential Cell Biology (© Garland Science 2010)
Proteins Can Assemble into Filaments, Sheets, or Spheres
Simian virus
microtubule
Figure 4-25 Essential Cell Biology (© Garland Science 2010)
Some Types of Proteins Have Elongated Fibrous Shapes
HOW PROTEINS WORK
• All Proteins Bind to Other Molecules• The Binding Sites of Antibodies Are Especially
Versatile• Enzymes Are Powerful and Highly Specific
Catalysts• Lysozyme Illustrates How an Enzyme Works• Most Drugs Inhibit Enzymes• Tightly Bound Small Molecules Add Extra
Functions to Proteins
Figure 4-27 Essential Cell Biology (© Garland Science 2010)
All Proteins Bind to Other Molecules
Figure 4-28a Essential Cell Biology (© Garland Science 2010)
Three dimentional structure
Binding Site/ active site
Figure 4-28b Essential Cell Biology (© Garland Science 2010)
Proteins interact with its ligand
Specific interaction!
1) Ligand fits into the binding site2)Because of combination of weak non-covalent bonds
hydrogen bondselectrostatic attractionvan der Waals attractionhydrophobic interactions
Figure 4-30 Essential Cell Biology (© Garland Science 2010)
Enzymes Are Powerful and Highly Specific Catalysts
Enzyme: proteins having catalytic (enzymatic) activity
Ligand is called substrate
Enzymes have catalytic domain/reaction site performing enzymatic reactions
Table 7-3 Essential Cell Biology (© Garland Science 2010)
Most Drugs Inhibit Enzymes
Figure 4-33 Essential Cell Biology (© Garland Science 2010)
Tightly Bound Small Molecules Add Extra Functions to Proteins
Co-enzymes and co-factors bind to proteins and change their activity
Hemoglobin protein, oxygen carrying protein
HOW PROTEINS ARE CONTROLLED
Genes can be expressed with different efficiencies
to regulate the amount of required protein
1 gene multiple RNA copies
rapid protein synthesis when required
The amount of proteins are regulated by expression and protein modifications!!!!!
Protein modifications:
Phosphorylation
Ubiquitination
Modifications are signals for degradation
Figure 4-38a Essential Cell Biology (© Garland Science 2010)
The catalytic activity of enzyme can be regulated by protein modifications
Phosphorylation – addition of phosphate group to protein
Phosphate group is linked only toTyrosineThreoninSerine amino acids
Enzymes are not active eveytime but activated when required
Figure 4-38b Essential Cell Biology (© Garland Science 2010)
The catalytic activity of enzyme can be regulated by protein modifications
Modifications change the 3-dimentional structure
Figure 5-27 Essential Cell Biology (© Garland Science 2010)
Modification of Histone
MethylationAcetylationPhosphorylationUbiquitination
Chromatin Remodeling
Figure 4-44a Essential Cell Biology (© Garland Science 2010)
Protein modifications regulate:
Activity of protein/enzyme
Lifetime/amount of protein
Location of proteins
Figure 4-34 Essential Cell Biology (© Garland Science 2010)
The Catalytic Activities of Enzymes Are Often Regulated by Other Molecules
Negative feedback Positive Feedback
Substrate inhibit enzyme Subtstrate increase the amount of active enzymeby binding to enzyme
Figure 4-17 Essential Cell Biology (© Garland Science 2010)
Proteins Have Several Levels of Organization
Proteins: long peptide chain
Parts of this long chain called protein domain, specific function
DNA binding domain
Protein-protein interaction domain
Catalytic domain
Transmembrane domain
Allosteric Enzymes Have Binding Sites That Influence One AnotherThe activity of Allosteric Enzymes regulated by other molecules
Bio-Engineering