Purchase this article with an account.
T.C. Edrington, V, P. Yeagle, K. Boesze–Battaglia; High Resolution Structural Studies On Peripherin–2, An Integral Membrane Protein Of The Retinal Rod Cell . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3733.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Peripherin–2 is a tetraspannin transmembrane protein, implicated in retinitis pigmentosa and localized in retinal rod outer segment disk membranes, whose complete 3–dimensional structure is the goal of this nuclear magnetic resonance (NMR) study.
The 63–residue C–terminal extramembraneous region of peripherin (PERCTER) is crucial to peripherin–mediated fusion.The first target of our structural analysis is the PERCTER, expressed and labeled with 15N, and subjected to structural determination by solution NMR. For this analysis, 3–dimensional HSQC–NOESY and HSQC–TOCSY experiments were utilized, along with 2–dimensional 1H NOESY and TOCSY experiments at various mixing times. This analysis is followed by a similar study of the PERCTER in the presence of a membrane–mimetic, DPC micelles.
The solution structure of the PERCTER that emerges from the NMR data contains considerable alpha–helix at the amino terminus (near the membrane) and is disordered at the C–terminus. In the presence of the membrane mimetic, detergent micelles, the PERCTER becomes more structured.
Peripherin–2 promotes membrane fusion events with rod cell membranes during the rod outer segment disk renewal processes. Several mutations in this C–terminal region have been linked to various forms of retinal degenerative disease. Interestingly, our results reveal that about half of the C–terminus is structured and the other half is unstructured in solution. These data collectively suggest that this portion of peripherin–2 biologically responds to interactions with membranes (and likely with other proteins) by becoming more structured. It is possible that in some RP mutations this ability to take on a biologically relevant conformation is impaired.
This PDF is available to Subscribers Only