7. 11. 2018

Arnošt Mládek: 
Charting the sequence preference for protein-membrane interactions

Abstrakt:

Lipids are well known for their amphipathic nature and their capacity to form
membrane bilayers. Their structures are diverse because of their distinct
chemical backbones, which are composed of glycerol in the case of the
glycerolipids and glycerophospholipids, sphingoid long-chain bases for the
sphingolipids and isoprene for the sterols. Lipid localization is tightly
regulated and shapes the unique function and properties of every cellular
membrane. The accumulation of discrete phosphatidylcholine, phosphoinositide,
glycerophospholipid, and various other species defines the identity of the
organelle and locally regulates the organization of cellular membranes into
microdomains. Lipids function predominantly through their interactions with
proteins. Indeed, protein–lipid interactions are involved in all biological
processes and are of paramount interest in pharmaceutical discovery, as 60% of
drug targets are located at the cell surface or in other cellular membranes.
Membrane proteins account for one-third of the full proteome. However, research
into the mechanisms that are used by lipids to modulate protein structure,
function, affinity has been restricted to a small number of proteins. This gap
in our knowledge is due to a lack of methods that are amenable to
systematically charting protein–lipid interactions, and a technological effort
similar to the one made for DNA–protein and RNA–protein interactions is now
needed for lipids.