Week 2

Amino acid: protein building block, 20

• Amine group, central carbon bonded to H and R-group, carboxyl group

• Peptide bonds: bonds amino acids via condensation reaction between carboxyl and amino group, C-N single bond that behaves like double

Anfinsen experiment: proved that primary sequence determines protein shape/structure

• Purified protein isolated from cells exposed to high concentration of urea

• Caused denaturing of protein down to its primary structure

• Removed denaturing agents and protein folded back into shape

• Basically the amino acids sequencing for structure was denatured, causing it to break its secondary/tertiary structure

Structures of proteins:

• Primary: unique sequence of amino acids

  • Order of R-groups matter because R-groups affect size, shape, reactivity, solubility

• Secondary: H-bonds between amino group and carboxyl group on amino acid backbone causing folding into a-helix or b-pleated

• Tertiary: 3D shape of protein, bonds and other interactions between R-groups or R-groups and peptide-bonded backbone

• Quaternary: interactions between multiple protein subunits, specifically between R-groups or between peptide-bonded backbone of diff polypeptides

Atomic interactions affecting tertiary structure:

• H-bonds: between R-group and carbonyl, determines secondary structure

• Hydrophobic effect: hydrophobic clustering to avoid water in the interior, water connected by H-bonds which is very dynamic/many possibilities, disruption is highly costly

  • Think nonpolar R-groups cluster together in hydrophobic core while polar R-groups are on outside H-bond with water

• Covalent bonding: disulfide bonds between R-groups

• Ionic bonding: between R-groups with opposite charges

EGFR protein: membrane spanning protein that causes for cell growth

Noncovalent interactions:

• Used to fold up single polypeptide

• Allow multiple polypeptide subunits to stably interact and form a complex protein (quaternary structure)

• Allow interactions between a protein and other molecules (different protein x different type of molecule sugar steroid ATP DNA mineral etc.)

Enzymes: binding sites are highly specific and binds via noncovalent interactions

Potassium channel: example of how channels are selective

• K+ hydrated by in aq solution, channel has affinity for it and pulls K+ by breaking hydrated bonds and providing needed bonds in channel, specific (e.g: Na+ too small to pass)

Conformation change: some proteins adopt two different shapes

• Transport protein conformation change allows solute passage (sodium-potassium pump)

• EGF Receptor conformation change allows dimerization

  • 1. Ligand binds 2. EGFR protein changes from A to B conformation 3. In B conformation, two molecules “bind” to each other 4. Causes a further conformational change in the internal domain which activates enzymatic activity

• Can modify protein binding (sodium-potassium pump)

• Can shut enzymes off (active to inactive)

• Can enhance enzyme-substrate interactions

  • Molecular recognition (specificity for substrates) 

  • Facilitates a chemical reaction

In peptide bonded backbone:

• R-group orientation: side chains extend out for interactions

• Directionality: N-terminus to C-terminus (anime group to carboxyl group)

• Flexibility: peptide bonds do not rotate but single bonds can

Oligopeptide/peptide: chain of <50 amino acids

Polypeptides: chains of 50+ amino acids

Protein: chain of amino acids, complete + functional form of molecule 

Dimers: proteins with 2 polypeptide subunits (homo/hetero depending on identicality of subunits)

Myoglobin/hemoglobin: 1/4 subunits 

Molecular chaperones: special proteins facilitate protein folding

• Prevents clumping of non-polar (hydrophobic) R-groups by attaching to them beforehand

Protein shapes are flexible:

• when inactive often flexible

• Protein folding regulated since protein function depends on shape (protein folding only begins after binding to molecules during signaling event) 

Prions: proteinaceous infectious particles

• Induces protein folding

• Occurs when infection prions bind to normal ones, causing conformational change 

Protein functions include…

• Catalysis: proteins specialized to catalyze via enzymes

• Structure: structural proteins make up body components + form internal skeleton of individuals + keeps red blood cells flexible in their normal disc-like shape

• Movement: motor/contractile proteins

• Signaling: proteins carry/receive signals 

• Transport: proteins allow particular molecules to enter/exit cells

• Defense: antibody proteins attack/destroy viruses