Background: Both backbone hydrogen bonding and interactions between sidechains stabilize β sheets. Cross-strand interactions are the closest contacts between the sidechains of a β sheet. Here we investigate the energetics of cross-strand interactions using a variant of the B1 domain of immunoglobulin G (IgG) binding protein G (β1) as our model system. Results: Pairwise mutations of polar and nonpolar residues were made at a solvent-exposed site between the two central parallel β strands of β1. 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 β sheets. We propose that cross-strand sidechain interactions specify correct strand register and ordering through the energetic benefit of optimally arranged pairings.
Submitter: Marie Ary
Submission Date: Feb. 22, 2017, 5:33 p.m.
|Number of data points||268|
|Assays/Quantities/Protocols||Experimental Assay: ΔGu (63°C) ; Experimental Assay: ΔHm pH5.2 ; Experimental Assay: ΔΔGu (25°C) ; Experimental Assay: ΔΔGu (63°C) ; Experimental Assay: Tm pH5.2 ; Experimental Assay: ΔΔGu (46°C) ; Experimental Assay: ΔHm pH7.2 ; Experimental Assay: Tm pH7.2 ; Derived Quantity: ΔΔΔGu (25°C) ; Derived Quantity: ΔΔΔGu (46°C)|
|Libraries||Thermodynamic parameters for variants with charged residues at parallel cross-strand site (pos 6,53) (Table 1) ; Thermodynamic parameters for variants with polar and non-charged residues at parallel cross-strand site (pos 6,53) (Table 2) ; ΔGu for non-charged and polar mutants paired with Ala at pH 5.2, 63 C (from Methods)|