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Updated: Aug 2, 2026

Real-time Observation of the DNA Strand Exchange Reaction Mediated by Rad51
Published on: February 13, 2019
Sidechain interactions in parallel beta sheets: the energetics of cross-strand pairings
J S Merkel1, J M Sturtevant, L Regan
1Department of Molecular Biophysics and Biochemistry, Yale University, PO Box 208114, New Haven, CT 06520-8114, USA.
Background:
Both backbone hydrogen bonding and interactions between sidechains stabilize beta sheets. Cross-strand interactions are the closest contacts between the sidechains of a beta sheet. Here we investigate the energetics of cross-strand interactions using a variant of the B1 domain of immunoglobulin G (IgG) binding protein G (beta1) as our model system.
Results:
Pairwise mutations of polar and nonpolar residues were made at a solvent-exposed site between the two central parallel beta strands of beta1. Both stabilizing and destabilizing interactions were measured. The greatest stabilizations were observed for charge-charge interactions. Our experimental study of sidechain interactions correlates with statistical preferences: residue pairs for which we measure stabilizing interaction energies occur together frequently, whereas destabilizing pairs are rarely observed together.
Conclusions:
Sidechain interactions modulate the stability of beta sheets. We propose that cross-strand sidechain interactions specify correct strand register and ordering through the energetic benefit of optimally arranged pairings.
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