Introductory Lecture 1
Self-organization of biological systems:
• self-assembly into compartments
• active transport
• molecular specificity
Cell types:
1. Cells are fundamental units of life
2. Cells use chemical or solar energy to function, grow, and reproduce
3. Cells are macromolecular factories
4. Cells move, divide (mitosis), and sense environmental conditions
Courtesy of Dr. Julian Heath.
©1982. Used by permission of Jones and Bartlett Publishers, Sudbury MA.
Prokaryotic cells
©1993. Used by permission of Springer-Verlag.
©1993. Used by permission of Springer-Verlag.
Eukaryotic cells
Mitochondria are organelles that
metabolize conversion of chemical
energy from food into ATP.
(b) ©1980. Used by permission of Elsevier Science.
Chromatin and cell nucleus
Felsenfeld & Groudine, Nature 2003
Chromatin under the microscope
High-resolution image of
a human chromosome
Section of a
chromosome:
central scaffold +
lateral loops
Electron micrograph of D.Melanogaster
chromatin: arrays of regularly spaced
nucleosomes, each ~80 A across.
Structure of the nucleosome core particle (NCP)
Left-handed superhelix: 1.84 turns, 147 bp, R = 41.9 A, P
= 25.9 A. PDB code: 1kx5
T.J.Richmond: K.Luger et al. Nature 1997 (2.8 Ǻ); T.J.Richmond & C.A.Davey Nature 2003 (1.9 Ǻ)
Chromatin-remodeling enzymes and posttranslational modifications
Figure 1. One potential scenario by which MeCP2 and the
SWI/SNF complex might cooperate in establishment or
maintenance of transcriptional repression at a methylated locus.
Paul A. Wade, Nature Genetics 37, 212 - 213 (2005)
Golgi apparatus and endoplasmic reticulum
 ER: synthesis of proteins, lipids and steroids,
metabolism of carbohydrates,
regulation of calcium concentration, etc.
 Golgi apparatus: modifying, sorting, and packaging
macromolecules for cell secretion (exocytosis)
or use within the cell.
Diagram of secretory process from endoplasmic
reticulum (orange) to Golgi apparatus (pink). 1.
Nuclear membrane; 2. Nuclear pore; 3. Rough
endoplasmic reticulum (rER); 4. Smooth
endoplasmic reticulum (sER); 5. Ribosome attached
to rER; 6. Macromolecules; 7. Transport vesicles; 8.
Golgi apparatus; 9. Cis face of Golgi apparatus; 10.
Trans face of Golgi apparatus; 11. Cisternae of lipids
Molecular “parts list”
Molecular composition of bacterial cells by weight:
Small molecules
water
amino acids, sugars, fatty acids, ions
74%
70%
4%
Macromolecules
proteins
RNA
DNA
lipids
polysaccharides
26%
15%
6%
1%
2%
2%
©1991 Larry Gonick.
©1982, American Association for the Advancement of Science. Used by permission.
20 types of amino acids in proteins
Protein Data Base accession code 1VII ({C.J. McKnight, D.S. Doering, P.T. Matsudaira, P.S. Kim, J. Mol. Biol. 260 126 (1996)).
Protein 3D structure
Protein Data Bank (PDB) http://www.rcsb.org
Elastic rod model
DNA looping induced by a Lac repressor tetramer
Protein Data Base accession code 1EHZ (H. Shi and P.B. Moore, RNA 6 1091 (2000)).
Fatty acids
D-glucose molecule, C6H12O6
Cellulose (polysaccharide)
©1993. Used by permission of Springer-Verlag.
Introductory Lecture 2
A single peptide (protein building block)
A polypeptide chain
A tyrosine (TYR) amino acid (one of 20 naturally
occurring amino acids)
Peptide torsion angles and secondary structure
• omega = 180 deg, phi & psi are variable
• minimize F({phi,psi}) – protein folding problem
Secondary structure elements: alpha & 3-10 helices
Secondary structure elements: beta sheets
Turns of the polypeptide chain
The Ramachandran plot
Side chain conformations
Protein 3D structure (second look)
Protein functions: enzymes, gene regulation, biosynthesis, etc.
Protein Data Bank (PDB) http://www.rcsb.org
Protein folding: I
Protein folding: II
Folding funnel
• Microtubules (25 nm): cytoskeleton
• Actin filaments (F-actin; 7 nm): actin cortex
Cell membranes are crowded: channels, receptors, pumps,
actin cortex attachment points
DNA & RNA
The genetic code
©1993. Used by permission of Springer-Verlag.
Eukaryotic promoter structure
Wray, G. A. et al. Mol Biol Evol 2003 20:1377-1419
©1993. Used by permission of Springer-Verlag.