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

Lander et al 3 x 10 9 base pairs

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

Little Alberts Fig Genes can be localized crudely by hybridizing a fluorescent nucleotide probe to chromosomes 2  m 6 distinct genes are probed in this image Seuss 1959

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

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

7 Little Alberts Fig © Garland publishing Gene activation involves regulatory regions

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

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

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 receptor 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” Greek, “first”

12 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

13 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

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

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