The Environment Around Salt Bridges in Helices
Carol HF Cheng and Russ B AltmanÝ Section on Medical Informatics Stanford University, MSOB x215 Stanford, CA 94305-5479 (415) 723-6979, Fax: (415) 725-7944 e-mail: {cheng, altman}@smi.stanford.eduABSTRACT
Background
The study of ionic interactions in alpha helices is critical for understanding their role in protein folding and stability. Previous analyses of salt bridges have been based on in-depth studies of specific bridges, or statistical studies of pooled ionic interactions. We have used a computational approach to compare the local biochemical environments surrounding four types of salt bridge in helices that differ in the identity and spacing of the interacting residues, in order to identify statistically significant differences in these environments.
Results
We find that (1) Glu-Arg (i, i+3) side chains tend to take on a standard geometry, while there is more structural variability for the other types, (2) Glu-Lys residues in an (i, i+4) conformation tend to be part of a three charge network, with the Glu residue surrounded by two areas of positive charge. This phenomenon was not observed in Glu-Lys bridges of the (i, i+3) conformation, or Glu-Arg bridges. Finally, (3) Glu-Lys (i, i+3) and Glu-Arg (i, i+4) bridges tend to be more solvent exposed than the other bridges tested.
Conclusion
There are significant differences in the environments surrounding salt bridges within helices differing in spacing and residue identities. Our results support the hypothesis that particular types of salt bridges have distinct functional roles, and that caution should be exercised in pooling observations from different types of salt bridges.
We make two appendices available in the electronic version of this paper. Appendix 1 contains a complete list of all significant properties found with p-levels < 0.005 for all the experiments described. Appendix 2 provides detailed definitions of the properties used by the program. In addition, we have included four kinemages, for each of the four types of salt bridge studied [ER(i+3), ER(i+4), EK(i+3), EK(i+4)], that allows the user to examine both the three-dimensional structures of the bridges as well as the location of significant properties in their associated volume of space.