Conserved thermodynamic contributions of backbone hydrogen bonds in a protein fold.
Backbone-backbone hydrogen-bonding interactions are a ubiquitous and highly conserved structural feature of proteins that adopt the same fold (i.e., have the same overall backbone topology). This work addresses the question of whether or not this structural conservation is also reflected as a thermodynamic conservation. Reported here is a comparative thermodynamic analysis of backbone hydrogen bonds in two proteins that adopt the same fold but are unrelated at the primary amino acid sequence level. With amide-to-ester bond mutations introduced by total chemical synthesis methods, the thermodynamic consequences of backbone-backbone hydrogen-bond deletions at five different structurally equivalent positions throughout the beta-alpha-alpha fold of Arc repressor and CopG were assessed. The ester bond-containing analogues all folded into native-like three-dimensional structures that were destabilized from 2.5 to 6.0 kcal/(mol dimer) compared with wild-type controls. Remarkably, the five paired analogues with amide-to-ester bond mutations at structurally equivalent positions were destabilized to exactly the same degree, regardless of the degree to which the mutation site was buried in the structure. The results are interpreted as evidence that the thermodynamics of backbone-backbone hydrogen-bonding interactions in a protein fold are conserved.
Department of Chemistry, Duke University, Durham, NC 27708, USA.
Min
M
Wang
Thomas E
TE
Wales
Michael C
MC
Fitzgerald
D000595:Amino Acid Sequence; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics; D013816:Thermodynamics
D011506:Proteins; D012097:Repressor Proteins