NMR studies of the fifth transmembrane segment of sarcoplasmic reticulum Ca2+-ATPase reveals a hinge close to the Ca2+-ligating residues.

Two recent X-ray structures have tremendously increased the understanding of the sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) and related proteins. Both structures show the fifth transmembrane span (M5) as a single continuous alpha-helix. The inherent structural and dynamic features of this span (Lys758-Glu785) were studied in isolation in sodium dodecyl sulfate (SDS) micelles using liquid-state nuclear magnetic resonance (NMR) spectroscopy. We find that a flexible region (Ile765-Asn768) is interrupting the alpha-helix. The location of the flexible region near the Ca(2+) binding residues Asn768 and Glu771 suggests that together with a similar region in M6 it has a hinge function that may be important for cooperative Ca(2+) binding and occlusion.