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A graphical method for analyzing distance restraints using residual dipolar couplings for structure determination of symmetric protein homo-oligomers.

Publication ,  Journal Article
Martin, JW; Yan, AK; Bailey-Kellogg, C; Zhou, P; Donald, BR
Published in: Protein Sci
June 2011

High-resolution structure determination of homo-oligomeric protein complexes remains a daunting task for NMR spectroscopists. Although isotope-filtered experiments allow separation of intermolecular NOEs from intramolecular NOEs and determination of the structure of each subunit within the oligomeric state, degenerate chemical shifts of equivalent nuclei from different subunits make it difficult to assign intermolecular NOEs to nuclei from specific pairs of subunits with certainty, hindering structural analysis of the oligomeric state. Here, we introduce a graphical method, DISCO, for the analysis of intermolecular distance restraints and structure determination of symmetric homo-oligomers using residual dipolar couplings. Based on knowledge that the symmetry axis of an oligomeric complex must be parallel to an eigenvector of the alignment tensor of residual dipolar couplings, we can represent distance restraints as annuli in a plane encoding the parameters of the symmetry axis. Oligomeric protein structures with the best restraint satisfaction correspond to regions of this plane with the greatest number of overlapping annuli. This graphical analysis yields a technique to characterize the complete set of oligomeric structures satisfying the distance restraints and to quantitatively evaluate the contribution of each distance restraint. We demonstrate our method for the trimeric E. coli diacylglycerol kinase, addressing the challenges in obtaining subunit assignments for distance restraints. We also demonstrate our method on a dimeric mutant of the immunoglobulin-binding domain B1 of streptococcal protein G to show the resilience of our method to ambiguous atom assignments. In both studies, DISCO computed oligomer structures with high accuracy despite using ambiguously assigned distance restraints.

Duke Scholars

Published In

Protein Sci

DOI

EISSN

1469-896X

Publication Date

June 2011

Volume

20

Issue

6

Start / End Page

970 / 985

Location

United States

Related Subject Headings

  • Streptococcus
  • Proteins
  • Protein Structure, Tertiary
  • Protein Multimerization
  • Protein Conformation
  • Nuclear Magnetic Resonance, Biomolecular
  • Models, Molecular
  • Escherichia coli
  • Diacylglycerol Kinase
  • Computer Simulation
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Martin, J. W., Yan, A. K., Bailey-Kellogg, C., Zhou, P., & Donald, B. R. (2011). A graphical method for analyzing distance restraints using residual dipolar couplings for structure determination of symmetric protein homo-oligomers. Protein Sci, 20(6), 970–985. https://doi.org/10.1002/pro.620
Martin, Jeffrey W., Anthony K. Yan, Chris Bailey-Kellogg, Pei Zhou, and Bruce R. Donald. “A graphical method for analyzing distance restraints using residual dipolar couplings for structure determination of symmetric protein homo-oligomers.Protein Sci 20, no. 6 (June 2011): 970–85. https://doi.org/10.1002/pro.620.
Martin, Jeffrey W., et al. “A graphical method for analyzing distance restraints using residual dipolar couplings for structure determination of symmetric protein homo-oligomers.Protein Sci, vol. 20, no. 6, June 2011, pp. 970–85. Pubmed, doi:10.1002/pro.620.
Journal cover image

Published In

Protein Sci

DOI

EISSN

1469-896X

Publication Date

June 2011

Volume

20

Issue

6

Start / End Page

970 / 985

Location

United States

Related Subject Headings

  • Streptococcus
  • Proteins
  • Protein Structure, Tertiary
  • Protein Multimerization
  • Protein Conformation
  • Nuclear Magnetic Resonance, Biomolecular
  • Models, Molecular
  • Escherichia coli
  • Diacylglycerol Kinase
  • Computer Simulation