Once upon a time …

The Cell Theory

Matthias Schleiden

The Nobel Prize in Chemistry 1907

Eduard Buchner

"I must tell you that I can make urea without the use of kidneys, either man or dog. Ammonium cyanate is urea."

Thomas Hunt Morgan was awarded the Nobel Prize in Physiology or Medicine in 1933.

So, Cell Biology is a woven cloth of So, Cell Biology is a woven cloth of

microscopy, biochemistry, genetics, & technology.microscopy, biochemistry, genetics, & technology.

Cell Biology lies as the foundation in a large part of Cell Biology lies as the foundation in a large part of our lives. our lives.

Your challenge is to find it.Your challenge is to find it.

Building the cell and making it run. Building the cell and making it run.

Protein, their structure and functionCompartmentsCompartment functions and intercompartment communicationElectrical The Power PlantCellular basis of tissue movementCell to Cell signalingCell from Cell- How and When

Protein Structure and Function

Enzyme: reaction catalysis, like protein degradation (pepsin), amino acid synthesis (tryptophan synthase)

Transport proteins: stomach (glucose carriers), blood stream (hemoglobin, albumin)

Motors: skeletal contraction proteins (myosin)

Storage: amino acids (ovalbumin), iron (ferritin)

Signaling: glucose (insulin and insulin receptors)

Gene regulation: DNA binding proteins (Lactose repressor)

Structural proteins: Hair ( keratin), intracellular cytoskeleton (tubulin)

It’s all about shape. The shape of a protein is related to its function.

The shape of a protein is specified by its amino acid sequence

Polypeptide backbone of amino acids with side chains that specify the unique property and folding pathway.

Mostly just 20 amino acids are used in polypeptide synthesis.Know the side chain type for each; not the structure.

Each protein has a unique 3D structure determined by the order of the amino acids.

Determining how the order of a.a. drives folding and determines the shape of a protein is the holy grail of protein chemistry.

Denaturation/renaturation studies have been informative.

Take home lesson: Proteins seek structures that have minimal free energy.

Non-covalent forces drive the folding pathway and maintain the final 3D structure. Hydrogen bonds, ionic bonds,and van der Waal attractions

The side chains drive the folding.

Hydrogen bonding is the most important. While low energy, … lots of ‘em.

Only a few structures out of many possibilities are stable

20n

109 seconds if you live to 65 years

1010390390 primary sequences for a 4 amino acid polypeptide primary sequences for a 4 amino acid polypeptide

Misfolded proteins can lead to neurodegenerative diseases.

Mad Cow Alzheimer’s and Huntington’s

…also prion diseases like BSE (cows), Scrapie (sheep), CFJ (humans)

Parallel or antiparallel?Silk, antifreeze, etc

Hair, hair, long, beautiful hair…skin too

Protein Structure hierarchy

Primary structure (sequence the protein- the first was insulin in ‘55, actually

easier to sequence the gene and deduce the protein sequence.)

Secondary Structure(alpha helix, beta sheet)

Tertiary (jelly roll, beta barrel, zinc fingers, coiled coil)

Quaternary Structure(homo-, hetero-, dimers, trimers, tetramers, etc)

What is in a domain?A domain by any other domain would smell as sweet?

Take for example: hemoglobin, four oxygen carrier, heterotetramer