Four major noncovalent bonds that help protein folding1. Ionic bond 2. van der Waals 3. Hydrogen bond, 4.
Hydrophobic force
Hydrophobic “forces”
The importance of hydrogen bond
Folding and Refolding
Secondary structures helix and sheet
Coiled-coil structure -keratin
Two types of sheet
structures
Src Kinase The combination of -
helix and -sheets
Classification of protein familiesTwo serine proteases
Two homeodomains from different species (yeast 2, green; drosophila engrailed protein, red)
Domains and ModulesDomain shuffling
Calcium binding domain
Kringle domain
Module Examples
The combination of Modules
Design Strategy
Weak FRET
Phosphatase
Strong FRET
433 nm
527 nm
433 nm
490 nm
ECFP(1-227) SH2(from c-Src) Substrate EYFPLinker
Src Activation
Protein Subunits
Hydrophobic forces
Hemoglobin
Protein assemblies
Actin Filaments
Disulfide bonds
Extracellular matrix protein are covalently cross-linked by
Disulfide bonds
Hexagonally packed globular protein subunits can form flat sheets
Self-AssemblyTobacco mosaic virus (TMV)
Electron Micrograph
Model Structure
The formation of Virus shell
X-Ray Crystallography of different virus(A) Tomato bushy stunt virus (B) poliovirus (C) simian virus
40 (SV40) (D) satellite tobacco necrosis virus
Three mechanisms of length determination for self-assembly
Protein assembly aided by assembly factors(insulin assembly)
Protein Functions
• Protein Binding• Protein conformation • Antibody • Enzyme and substrate • Catalytic Reaction • Kinase and phosphatase• GTPase, GEF, GAP• Motor protein• Membrane-bound protein
Protein binding
Protein binding sites
Protein binding siteCyclic AMP
Protein binding sites1. Restriction of water entrance
2. Alteration of reactivity
Sequence Comparison to find conserved binding sites
Sh2 domain
Three ways for two proteins to bind
Antibody
Noncovalent bonds and protein interactions
Binding Energy and Equilibrium constant
Enzyme Kinetics Read Panel 3-3, page 165
Enzymes lower the activation energy to accelerate chemical reactions
Lysozyme actionsBending of the polysaccharide bond
Steps of lysozyme actions
Strategies of enzyme catalysis
Feedback inhibitions
Coupled regulation: Positive Regulations
Coupled regulation: negative Regulations
Coupled regulation on multiple subunits
Aspartate transcarbamoylase
Kinase and phosphatase
Kinase Domain
Kinase families
Cyclin-dependent Kinase (CdK):Signal integrator
threonine
tyrosine
Src Kinase
Multiple Inputs for Src Kinase activation
GTPases
Ras Structure:One kind of GTPases
Phosphorylation and GTP binding regulations
EF-Tu and its regulation of tRNA
Motor Protein RegulationMyosin on Actin and Kinesin on Microtubules