Proteins Protein Structures and Shapes Protein Functions

Protein Structures and Shapes Amino acids Peptide bonds alpha helix and beta sheet Domains and Modules Classification of Families Protein Assembly

Amino Acids form polypeptide through peptide bond

Structural Components of a protein

The 20 Amino Acids 2 negative, 3 positive, 5 non-charged polar, 10 nonpolar Read Page , panel 3-1

Limitations on the bond angles Ramachandran plot

Four major noncovalent bonds that help protein folding 1. 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 families Two serine proteases

Two homeodomains from different species (yeast  2, green; drosophila engrailed protein, red)

Domains and Modules Domain 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) SubstrateEYFP Linker 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-Assembly Tobacco 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 site Cyclic AMP

Protein binding sites 1.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 actions Bending 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 Regulation Myosin on Actin and Kinesin on Microtubules

Membrane Protein Calcium Pump on Sarcoplasmic reticulum