Residual Dipolar Couplings in Structure Determination of Biomolecules

Abstract

Contents 1. Introduction 3519 2. Origin of Residual Dipolar Couplings and Complementary Observables 3520 2.1. Residual Dipolar Couplings (RDCs) 3520 2.2. Chemical Shift Anisotropy (CSA) 3521 2.3. Pseudocontact Shifts in Paramagnetic Systems 3522 2.4. Cross-Correlated Relaxation 3522 3. Alignment of Samples 3523 3.1. Bicelles 3523 3.2. Bacteriophage 3523 3.3. Polyacrylamide Gels 3524 3.4. Other Media 3524 3.5. Practical and Theoretical Considerations 3524 4. RDC Data Acquisition 3526 4.1. One-Bond H N −N and C−H RDCs 3526 4.2. Other Protein Backbone RDCs 3528 4.3. One-Bond C−C and C−H RDCs in Protein Side-Chains 3531 4.4. Proton−Proton RDCs 3531 5. Structural Interpretation of RDCs 3532 5.1. Additional Constraints in Structure Determination and Refinement 3533 5.2. Direct Structure Determination 3533 5.3. A Tool for Structure Validation or Homology Searches 3535 5.4. Orientational Relationships between Components 3535 6. Limitations and Future Directions 3537 7. Abbreviations 3537 8. Acknowledgments 3538 9. References 3538

Three‐dimensional structure of the weakly associated protein homodimer SeR13 using RDCs and paramagnetic surface mapping

“…For hetero-oligomeric complexes, of course, one can determine alignment tensors independently for each subunit and assemble a structure by rotating subunits to superimpose principal axis systems. 9,10,13,14,38 One of the primary limitations of the methods described is that the structure of the monomeric unit must be available. This structure could come from existing crystal structures that may not show the proper assembly for weak complexes, or it could come from NMR based structure determination.…”

“…9 They are measured as additions to scalar couplings in modified HSQC or TROSY spectra that occur under conditions of partial orientation of the complex in a magnetic field, and require no more prior work other than the assignment of the backbone resonances in these spectra. When a structure for the monomer unit of a homo-oligomeric complex is known (from NMR or X-ray studies), analysis of the RDCs provides information on the orientation of the alignment frame in terms of molecular coordinates.…”

A Refined Model for the Structure of Acireductone Dioxygenase from Klebsiella ATCC 8724 Incorporating Residual Dipolar Couplings

“…We now describe a refinement of the NiARD structural model that employs 1 H-15 N RDCs measured in two alignment media, 1-hexanol/ nonsymmetric polyol HO-(CH 2 O) 6 -(CH 2 ) 11 CH 3 (C12E5) (Ruckert and Otting, 2000) and filamentous phage (fd) (Hansen et al, 1998). The use of residual dipolar couplings (RDCs) has revolutionized the determination of solution structures of proteins by NMR (Prestegard et al, 2004;Tjandra et al, 1997).…”

“…The use of residual dipolar couplings (RDCs) has revolutionized the determination of solution structures of proteins by NMR (Prestegard et al, 2004;Tjandra et al, 1997). Unlike NOEs and J-coupling that are local constraints and not related to a single frame of reference, RDCs provide an independent structural parameter that relate to a single frame of reference provided by the order tensor.…”

Nuclear Magnetic Resonance-Based Modeling and Refinement of Protein Three-Dimensional Structures and Their Complexes

“…They can be measured in solution by weakly aligning the molecule using a variety of methods [30]. RDCs provide angular information between the internuclear vector for which they are measured and a set of globally defined axes in the molecule, namely those of the alignment tensor.…”