Strategies for dealing with conformational sampling in structural calculations of flexible or kinked transmembrane peptides.
Peptides corresponding to transmembrane (TM) segments from membrane proteins provide a potential route for the determination of membrane protein structure. We have determined that 2 functionally critical TM segments from the mammalian Na+/H+ exchanger display well converged structure in regions separated by break points. The flexibility of these break points results in conformational sampling in solution. A brief review of available NMR structures of helical membrane proteins demonstrates that there are a number of published structures showing similar properties. Such flexibility is likely indicative of kinks in the full-length protein. This minireview focuses on methods and protocols for NMR structure calculation and analysis of peptide structures under conditions of conformational sampling. The methods outlined allow the identification and analysis of structured peptides containing break points owing to conformational sampling and the differentiation between oligomerization and ensemble-averaged observation of multiple peptide conformations.
Rainey
Jan K
JK
Protein Engineering Network of Centres of Excellence and Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2H7, Canada. jan.rainey@dal.ca
Fliegel
Larry
L
Sykes
Brian D
BD
D008433:Mathematics; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry* / Q000235:genetics; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012985:Software Design; D013329:Structure-Activity Relationship
D008565:Membrane Proteins; D010455:Peptides