title: Sidechain interactions in parallel beta sheets: the energetics of cross-strand pairings.
abstract: 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.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, PO Box 208114, New Haven, CT 06520-8114, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Merkel
authors.forename: J M
authors.initials: JM
authors.lastname: Sturtevant
authors.forename: L
authors.initials: L
authors.lastname: Regan
mesh_terms: D002151:Calorimetry; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D008222:Lymphokines / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D029584:Prostatic Secretory Proteins; D013816:Thermodynamics
chemical_list: D008222:Lymphokines; D029584:Prostatic Secretory Proteins; C043076:beta-microseminoprotein; C013059:immunoglobulin-binding factors