Identification of a Protein Family Crucial for Membrane Asymmetry
To biochemists who deal with soluble proteins, the various membranes inside of a cell can often be treated as little more than nondescript barriers which their enzyme or receptor of interest might interact with only briefly during synthesis. Of course cell membranes are strikingly complex systems in and of themselves, and there is a fairly large field of research focused only on the study of membrane structure and organization.
In a recent (Open Access!!) paper from PNAS, the authors (from Tokyo University and JSTA) describe the “de-orphanization” of an entire family of proteins (an orphaned protein is one for which no function is known). The research in the paper expands the list of proteins involved in membrane remodeling - that is, changing the types of lipids which make up a given membrane. There are two steps to membrane remodeling. First a phospholipase clips off the group at the sn-2 position of the lipid, and then a lysophospholipid acyltransferase (LPLAT) replaces it with an alternate group. This newly identified family falls into the latter category of proteins.
To identify the proteins, the authors compared the sequences of known LPLATs with those of a family of unclear funtion, called the MBOATs. They expressed several of these MBOATs in cell lines, and monitored their expression patterns as well as signs of membrane remodeling.
The new family is interesting because it doesn’t contain any of the motifs which are common to previously identified LPLATs. Also, the study of this cycle of membrane remodeling (the Lands Cycle) is important, as the lipid cleavage products (fatty acids and lysophospholipids) are involved in critical signalling pathways such as inflammation. I also personally appreciate it when research clarifies the in vivo function of proteins. We already have an ever-expanding list of genomes (a listing of all the genetic material in an organism), and people are always working on proteomes (a list of all proteins expressed by a given genome), but it’s this de-orphanization of the proteins that really tells us what they are doing.
Since these newly identified LPLATs do not contain the canonical motifs, I think it would be very interesting to follow up on these studies with some more specific experiments designed to discover the mechanism by which they function. Of course, the best thing (and I am in no way biased here) would be a structure of at least one of these proteins.
