Wednesday 23 September 2009
to 17:00 at
Aron Hennerdal (SBC/CBR)
Alpha-helical membrane proteins consist of transmembrane (TM) segments that traverse the membrane with the N-terminal end at alternating sides of the membrane. This division of the chain into TM and non-TM segments along with the designations of the non-TM regions as either "inside" (cytosolic) or "outside" (extracellular/inside cellular organelles) is referred to as the "topology" of the membrane protein. The prediction of topology is a useful sub-problem in the overall structure prediction of alpha-helical membrane proteins.
In this work we attempt to add to the knowledge about the translocon and its workings' effects on membrane protein evolution. We attempt to shed light on some interesting features of membrane protein duplications, how they appear and how this knowledge is transferrable to other protein sequences.
Duplications in homologues to known structures of TM proteins were found using STRUCTAL (structural superposition) and SCAMPI (sequence-based profile-HMM alignment). Different scoring schemes of these methods were tried on a test set of known structures for their ability to find duplications. SCAMPI turns out to perform slightly worse, but acceptably, and was used for finding potential duplications in proteins of a number of genomes.
Results from the genome investigation show that the most common du- plication units are of 3- and 6-TM-regions respectively and that anti-parallel orientations - N-terminal end of the units on the same side of the membrane - of duplications in homologues are surprisingly common. In addition, a particu- larly interesting example, the acriflavine resistance protein (PDB 1oyeA), shows a distinct set of homologues of 3 and 6 TM-regions, which hints at a duplication and subsequent fusing in the distant past.