4. DNA
Contained in the nucleus
Arranged in 22 chromosomes, plus two
sex chromosomes
Two copies of each
99.9% identical to other humans, 98% to
chimp!
Around 2m DNA, enough to travel to sun
and back 600 times!
Therefore, very tightly packed
14. Protein interactions
Proteins can form interations:
– Proteins (complexes, oligomers)
– mRNA
– DNA
Proteins can bind to each other depending
on their relative charges and structures
19. We have used the yeast two-hybrid system to identify proteins that interact with the
intracellular portion of the hepatocyte growth factor (HGF) receptor (Met). We isolated a
human cDNA encoding a novel protein of 68 kDa, which we termed FAP68. This protein is
homologous to a previously described FK506-binding protein-associated protein, FAP48,
which derives from an alternative spliced form of the same cDNA, lacking an 85-nucleotide
exon and leading to an early stop codon. Here we show that epithelial cells, in which the
HGF receptor is naturally expressed, contain FAP68 and not FAP48 proteins. FAP68 binding
to Met requires the last 30 amino acids of the C-terminal tail, which are unique to the HGF
receptor. Indeed, FAP68 does not interact with related tyrosine kinases of the Met and
insulin receptor families. FAP68 interacts specifically with the inactive form of HGF receptor,
such as a kinase-defective receptor or a dephosphorylated wild type receptor.
Evidence
In vivo, endogenous FAP68 can be coimmunoprecipitated with the HGF receptor in the
absence of stimuli and not upon HGF stimulation. Thus, FAP68 represents a novel type of
effector that interacts with the inactive HGF receptor and is released upon receptor
phosphorylation. Free FAP68 exerts a specific stimulatory activity toward the downstream
target p70 S6 protein kinase (p70S6K). Significantly, nonphosphorylated HGF receptor
prevents FAP68 from stimulating p70S6K. These data suggest a role for FAP68 in coupling
HGF receptor signaling to the p70S6K pathway.
20. Future of molecular biology
Personalised medicine
Target-specific drugs (e.g. adipose tissue)
Gene therapy
Comparative genomics
21. References
Molecular biology information
– ‘Biology’, Campbell and Reece (6th Ed.), Very readable general biology textbook
– www.ebi.ac.uk/2can, good introduction to bioinformatics and molecular biology
– http://www.emc.maricopa.edu/faculty/farabee/BIOBK/BioBookTOC.html - online biology book
– http://biology-pages.info, good glossary/information site
– http://www.genomicglossaries.com/
– http://www.gene.ucl.ac.uk/nomenclature/guidelines.html, defines the nomenclature for
human genes
Databases
– www.ebi.uniprot.org, excellent protein sequence database
– www.ncbi.nih.gov, numerous protein/genome databases
– www.ensembl.org, information on genes/proteins/exons of completed genomes
– http://www.ebi.ac.uk/embl/, European gene sequence databank
– Michael Y. Galperin, The Molecular Biology Database Collection: 2005 update, NAR
– www.bioinfo.no/links, list of useful biological links
Gene/Protein naming conventions
– Bioinformatics. 2005 Jan 15;21(2):248-56. Epub 2004 Aug 27. Gene name ambiguity of
eukaryotic nomenclatures.Chen L, Liu H, Friedman C.
