Introduction

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.

Publications

  1. A graphical method for analyzing distance restraints using residual dipolar couplings for structure determination of symmetric protein homo-oligomers.
    Cite this
    Martin JW, Yan AK, Bailey-Kellogg C, Zhou P, Donald BR, 2011-06-01 - Protein science : a publication of the Protein Society
  2. A geometric arrangement algorithm for structure determination of symmetric protein homo-oligomers from NOEs and RDCs.
    Cite this
    Martin JW, Yan AK, Bailey-Kellogg C, Zhou P, Donald BR, 2011-11-01 - Journal of computational biology : a journal of computational molecular cell biology

Credits

  1. Jeffrey W Martin
    Developer

    Department of Computer Science, Duke University, United States of America

  2. Anthony K Yan
    Developer

  3. Chris Bailey-Kellogg
    Developer

  4. Pei Zhou
    Developer

  5. Bruce R Donald
    Investigator

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Summary
AccessionBT006489
Tool TypeApplication
Category
PlatformsLinux/Unix
Technologies
User InterfaceTerminal Command Line
Download Count0
Submitted ByBruce R Donald