Once upon a time …
Matthias Schleiden
The Cell Theory
"I must tell you that I can make urea without the use of kidneys,
either man or dog. Ammonium cyanate is urea."
Eduard Buchner
The Nobel Prize in Chemistry 1907
Thomas Hunt Morgan was awarded the Nobel Prize in
Physiology or Medicine in 1933.
So, Cell Biology is a woven cloth of
microscopy, biochemistry, genetics, & technology.
Cell Biology lies as the foundation in a large part of
our lives.
Your challenge is to find it.
Building the cell and making it run.
Protein, their structure and function
Compartments
Compartment functions and intercompartment communication
Electrical
The Power Plant
Cellular basis of tissue movement
Cell to Cell signaling
Cell from Cell- How and When
Protein Structure and Function
Enzyme: reaction catalysis, like protein degradation (pepsin),
amino acid synthesis (tryptophan synthase)
Structural proteins: Hair (a keratin), intracellular cytoskeleton
(tubulin)
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)
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
n
20
10390 primary sequences for a 4 amino acid polypeptide
9
10
seconds
if you live to 65 years
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