Lesk: Introduction to Genomics 
Answers to end-of-chapter exercises
Figures from the bookLesk: Introduction to Genomics
Chapter 02
Please note: the filesize of some of the rotating structures is over 1MB and they may take a moment to view
Page 101, Fig 2.17
A fragment of fibronectin, a modular protein, showing four tandem domains [1FNF].
rotating [784KB];
static
Page 102, Fig 2.18
G-protein-coupled receptors (GPCRs) are a large family of transmembrane proteins involved in signal transduction into cells. They share a substructure containing seven transmembrane helices, arranged in a common topology. This figure shows the only experimentally determined mammalian GPCR structure, bovine opsin [1H68]. This molecule senses light and generates a nerve impulse.
The seven-helical structure is common to the family of GPCRs. The helices traverse the
membrane, with loops protruding outside and inside the cell. This figure shows a view parallel
to the membrane, with the extracellular side at the top. The transmembrane region is generally
flanked by N- and C-terminal domains. The N-terminal domain is always outside the cell and the
C-terminal domain always inside.
GPCRs constitute the largest known family of receptors. The family is as old as the eukaryotes
and is large and diverse. Mammalian genomes contain ∼1500-2000 GPCRs, accounting for
about 3-5% of the genome. A similar fraction of the C. elegans genome codes for GPCRs.
Some GPCRs are involved in sensory reception, including vision, smell and taste. Some, like
opsin and bacteriorhodopsin, bind chromophores. (Bacteriorhodopsin is not a signalling molecule
but a light-driven proton pump.) Others respond to extracellular ligands including hormones and
neurotransmitters.
As expected from the structure, in many groups of GPCRs the sequences of the helical regions
diverge less than the sequences of the loops. It is the loops that determine the specificity of the ligand, and of the G-protein partner.
The common mechanism of function of GPCRs is a conformational change, induced by
receptor binding or light absorption. The activated state of the GPCR interacts with an
intracellular G protein, triggering a signal cascade. As there are substantially more GPCRs than G proteins, many GPCRs must interact with a single G protein. For instance, all odorant receptors interact with the same G protein α-subunit.
GPCRs are the targets for many drugs used in the treatment of high blood pressure, asthma,
allergies and other conditions. The large number of related GPCRs is a challenge to the design of drugs that bind to a unique target. Many drugs have undesired side effects because of imperfect specificity.
rotating [1.31MB];
static
View print version