Proline residues thermodynamics

While the residue stability constants are purely thermodynamic quantities defined for all residues, the protection factors also contain non-thermodynamic contributions and are defined only for a subset of residues. For example, proline residues lack the amide group and therefore are not included. From a statistical standpoint, the protection factor for any given residue] can be defined as the ratio of the sum of the probabilities of the states in which residue j is closed, to the sum of the probabilities of the states in which residue] is open ... 

Interestingly, it appears that it is easier to induce the formation of a helical hairpin with the tight turn on the lumenal side of the ER membrane than one with the opposite orientation (cytoplasmic turn) i.e., whereas a single Pro is enough to convert the 40-residues long poly (Leu) stretch to a helical hairpin with a lumenal turn, three consecutive prolines are needed for a helical hairpin with a cytoplasmic turn to form (Saaf et al., 2000) (Fig. 2B). If one only considers simple protein—lipid interactions there is no obvious thermodynamic reason why this should be so instead, we favor the view that this reflects a constraint on helical hairpin structure imposed by the Sec machinery. 

Of the 49 protected residues, 44 are correctly predicted to exhibit protection. In addition 62 are correctly predicted to show no protection 6 are prolines, 26 are solvent accessible, and 30 (residues 9, 10, 35, 41, 44-46, 49, 50, 52, 54, 55, 57-60, 77-80, 83, 85-88, 118, 119, 121, 138, and 139) are predicted to have protection factors below the experimental limit of detection. This relatively large number of residues beyond experimental detection is primarily due to the high temperature (37°C) at which the experiments were performed (Loh et al., 1993). This gives a total of 100 residues (excluding prolines) or 78% for which the prediction matches the experimental results. Of the 29 mispredictions, the vast majority (24) represent cases in which protection was predicted but not observed. This pattern suggest that many of those residues may indeed be thermodynamically stable but able to exchange by adifferent mechanism. For those residues that... 

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