2.B.45.  The pH low insertion peptide (pHLIP) Family 

The applications of the pH low insertion peptide (pHLIP) in cancer diagnosis and cross-membrane cargo delivery have been reported. With its origin as the transmembrane (TM) helix C of bacteriorhodopsin, pHLIP is also an important model for understanding how pH can affect the folding and topogenesis of a TM alpha-helix. Protonations of multiple D/E residues transform pHLIP from an unstructured coil at the membrane surface (known as state II, at pH >/= 7) to a TM alpha-helix (state III, pH) has been described (Otieno et al. 2018).



Otieno, S.A., S.Z. Hanz, B. Chakravorty, A. Zhang, L.M. Klees, M. An, and W. Qiang. (2018). pH-dependent thermodynamic intermediates of pHLIP membrane insertion determined by solid-state NMR spectroscopy. Proc. Natl. Acad. Sci. USA 115: 12194-12199.