Hi Justin, Since GPCRs are polytopic a-helical transmembrane proteins, it is very likely that (1) insertion into the membrane is primarily performed by the Sec61 complex AKA translocon and (2) targeting to the membrane would be controlled by the signal recongition particle and its receptor. the latter implies that a N-terminal signal sequence (that may very well be the first TM of a GPCR) would control the insertion process. Does your favorite GPCR have a predicetd signal sequence? Sec61 in theory contributes to signal sequence orientation according to the positive-inside end rule....but as for any rule they are exceptions.
there is a set of excellent papers dissecting this mechanism by Skach WR NSMB (2009) 16:6 606-12 (review) Pitonzo & Skach Mol Biol Cell (2009) 20(2) 685-698 (article) Sadlish H & Skach NSMB (2005) 12(10) 870-878 (article) Sadlish and Skach J Membrane Biol 202 115-126 (2004) (review) You may also want to look in the work of the group of Art Johnson (paper by Woolhead et al) describing the insertion process of aquaporin by the sec61 complex. they are polytopic a-helical membrane proteins and you may want to look into these articles since they dissect the process of TM insertion, orientation and protein maturation quite well. Hope this helps, Best regards -- Pascal F. Egea, PhD Assistant Professor UCLA, David Geffen School of Medicine Department of Biological Chemistry 314 Biomedical Sciences Research Building office (310)-983-3515 lab (310)-983-3516 email pe...@mednet.ucla.edu
