Gas-phase behavior of noncovalent transmembrane segment complexes

Specific helix oligomerization between transmembrane segments (TMSs) is often promoted by motifs like GxxxG. Disruption of this motif in the transmembrane segments of vesicular stomatitis virus G-protein and of glycophorin A results in a reduced dimerization level studied by in vivo systems like ToxR. This paper reports the influence of sequence motifs like GxxxG in solution and the gas phase. The transmembrane segments may behave differently in the gas and liquid phase, because of the absence of surrounding solvent molecules in the gas phase. Comparison of experiments depending on peptide properties performed in the gas and liquid phase discloses that the peptides retain 'some memory' of their liquid-phase structure in the gas phase. A direct correlation has been found between helicity in solution as determined by circular dichroism and dimerization in the gas phase monitored by electrospray mass spectrometry. These results show that a proper folding in solution is required for oligomerization. On the other hand, sequence-specific oligomerization depending on the GxxxG motif was not observed with the mass spectrometric detection. Further on, neither concentration-dependent complex studies nor studies regarding complex stability in the gas phase - via collision-induced dissociation (CID) - led to sequence-specific differences. Finally, the findings show that in mass spectrometric measurements noncovalent interactions of studied TMSs is rather more dependent on the secondary structure and proper folding than on their primary structure.