Contribution of CaH...O hydrogen bonds to membrane protein stability

Madhusoodanan Mottamal

Biochemistry, 44:1607-13 (2005)

CaH...O hydrogen bonds in glycophorin and bacteriorhodopsin


Structural analyses of membrane proteins reveal a large number of CaH...O contacts between transmembrane helices, presumed to be hydrogen bonds. Recent experiments produced conflicting results for the contribution of such hydrogen bonds to membrane protein stability. An FTIR study estimated an energy of -0.88 kcal/mol for the G79.CaH...I76.O hydrogen bond in glycophorin A, whereas a mutagenesis study showed that the A51.CaH...T24.Og hydrogen bond does not stabilize bacteriorhodopsin. In this work we reconciled these results using molecular mechanics calculations and an implicit membrane model (IMM1). With explicit hydrogen atoms, the potential energy of the G79.CaH...I76.O interaction in GpA ranges from -0.54 to -0.9 kcal/mol and its contribution to stability (effective energy) from -0.49 to -0.83 kcal/mol, depending on the structural model used. The average values of these quantities in GpA-like motifs are similar. In BR, the corresponding numbers for the A51.CaH...T24.Og interaction are +0.15 kcal/mol and +0.32 kcal/mol. The difference results from the different arrangement of the interacting groups and specifically the position of the acceptor with respect to the Ca and N atoms. This conclusion likely applies to soluble proteins as well.