A hybrid NMR/SAXS-based approach for discriminating oligomeric protein interfaces using Rosetta

作者：Rossi Paolo; Shi Lei; Liu Gaohua; Barbieri Christopher M; Lee Hsiau Wei; Grant Thomas D; Luft Joseph R; Xiao Rong; Acton Thomas B; Snell Edward H; Montelione Gaetano T; Baker David; Lange Oliver F; Sgourakis Nikolaos G^*

来源：Proteins: Structure, Function, and Genetics , 2015, 83(2): 309-317.

DOI：10.1002/prot.24719

• protein complex
• nuclear magnetic resonance spectroscopy
• CS-Rosetta modeling
• residual dipolar coupling
• small-angle X-ray scattering

Oligomeric proteins are important targets for structure determination in solution. While in most cases the fold of individual subunits can be determined experimentally, or predicted by homology-based methods, protein-protein interfaces are challenging to determine de novo using conventional NMR structure determination protocols. Here we focus on a member of the bet-V1 superfamily, Aha1 from Colwellia psychrerythraea. This family displays a broad range of crystallographic interfaces none of which can be reconciled with the NMR and SAXS data collected for Aha1. Unlike conventional methods relying on a dense network of experimental restraints, the sparse data are used to limit conformational search during optimization of a physically realistic energy function. This work highlights a new approach for studying minor conformational changes due to structural plasticity within a single dimeric interface in solution. Proteins 2015; 83:309-317.

• 出版日期2015-2