Signal Transduction

• Channels• Enzyme-linked receptors

– Receptor tyrosine kinases– Tyrosine kinase associated receptors– Receptor tyrosine phosphatases– Transmembrane receptor S/T kinases– Transmembrane guanyl cyclase

• G-proteins

Channels

• Voltage-gated

• Ligand-gated

• Mechanosensitive

Allosteric effectors of protein structure/function

Mechanosensitive channels

• MscS

Conserved channel architecture

How does it work?

Tyrosine kinases

Insulin-mediated cascade

Small protein modules as signal adaptors

SH2 and SH3 motifs

SH3 domain binding

The multi-domain structure of enzymes

What happens to this enzyme when SH3 finds a partner?

Notice the change in the linker…

G-proteins

Nucleotide hydrolysis as a timing mechanism

Metals can be essential

Conformational changes drive cycling between GTP-GDP bound states

Inferring mechanism from structure

Catalytic mechanism

G binds to G

G is has a propellar structure

This interaction is regulated by other proteins

One result of signal transduction

Protein kinase A activation