1. An introduction to molecular biology . . .
Bi 150 Lecture 0
October 4, 2012
An introduction to molecular biology . . .
but you will learn the cell biology in this course

2. 3 x 109 base pairs
Lander et al

3. Males are XY; females are XX.
Humans have 22 pairs of chromosomes, plus the X and Y.
Males are XY; females are XX.
A. Each chromosome is “painted” with a unique combination of fluorescent dyes
B. We have arranged the chromosomes to form pairs.
© Garland; Little Alberts Fig 5-12

4. Genes can be localized crudely by
hybridizing a fluorescent nucleotide probe to chromosomes
2 mm
6 distinct genes are probed in this image
Little Alberts Fig 10-16
Seuss 1959

5. Complete DNA sequence as scripture (surf NCBI)
orthologs in other species
single-nucleotide polymorphisms (SNPs)
mutations that cause disease
chromosomal location
basic sequence
proteins that bind to the sequence and regulate expression
RNA splicing
RNA sequence
RNA abundance
protein sequence
protein function
protein structure

6. How much coding sequence is in the genome?
22,000 genes x 400 codons/protein x 3 bases/codon
= 26.4 million base pairs, or < 1% of the genome!
The remainder . . .
1. Repetitive elements (junk? selfish DNA?)
2. Regulatory regions
3. Introns

7. Gene activation involves regulatory regions
Little Alberts Fig. 8-15
© Garland publishing

8. untranslated sequences
Components of Expression
coding sequences
noncoding sequences
Gene (DNA)
exon
intron
transcription (mRNA synthesis)
splicing (introns removed)
messenger RNA (mRNA)
translated sequences
untranslated sequences
translation
protein

9. Protein synthesis and degradation
A. synthesis
B. degradation
“proteolysis”
protein + Greek, breakdown
Modified from Little Alberts Panel 2-5

10. the tRNA synthetase translates the genetic code, because it contacts
(a) the amino acid
(c) in some cases, other parts of the tRNA
(b) the anticodon loop

11. Most drug receptors are proteins.
a molecule on the cell surface or in the cell interior that has an affinity for a specific molecule (the ligand).
Latin,
“to tie”
Most drug receptors are proteins.
Greek, “first”

12. shortest: 9 longest: 5500 “peptide” or amide bonds 20 types link the
“backbone”
“main chain”
“a-carbons”
side chains
20 types
Little Alberts Figure 2-22
© Garland publishing

13. Proteins contain a few structural motifs:
a helices b sheets
(A protein viewer must be installed on your computer)
Hide side chains
Show H-bonds and distances
Show ribbons & arrows
Show side chains
Show Van der Waals radii

14. Most drug receptors are membrane proteins
nicotine,
another agonist
nicotinic
acetylcholine
receptor
Outside the cell
natural ligand
(agonist)
~ 100 Å
= 10 nm
Membrane = lipid bilayer
Inside the cell = cytosol
(view in ~1995)

15. Several ways to make an arch
Protein Folding vs. “Inverse Folding” = Computational Protein Design
Protein Folding
(no degeneracy)
Inverse Folding
(large degeneracy)
Set of All
Structures
Set of All
Sequences
Individual
amino acids
Several ways to make an arch

16. G protein-coupled receptor
membrane
A future Lecture
receptor t s q i
G protein
enzyme
channel
effector
kinase
phosphorylated
protein
cAMP
Ca2+
intracellular
messenger
cytosol
The pathway from a
G protein-coupled receptor
(GPCR) to
gene activation
nucleus
How fast?
10 s to days
How far?
Up to 1 m

17. Protein degradation is accomplished primarily by proteolytic enzymes
The genome encodes hundreds of proteolytic enzymes.
They vary in
-- sequence specificity for the “cut”
-- cellular expression
-- organelle of expression

18. Cells often mark proteins for proteolysis by attaching strings of the protein, ubiquitin.
strings of ubiquitiin
to be
proteolyzed
other
protein
modified from Little Alberts Fig 18-7

19. Controlled proteolysis takes place in the proteasome
shorter
modified from Little Alberts 1st edition Fig 7-32

20. Atomic-scale Structures
procaine
morphine
botulinum
toxin
nicotine
(Download to your computer;
Then open with Swiss-prot pdb viewer)