2MG4

Computational design and experimental verification of a symmetric protein homodimer


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 32 
  • Conformers Submitted: 10 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Computational design and experimental verification of a symmetric protein homodimer.

Mou, Y.Huang, P.S.Hsu, F.C.Huang, S.J.Mayo, S.L.

(2015) Proc Natl Acad Sci U S A 112: 10714-10719

  • DOI: https://doi.org/10.1073/pnas.1505072112
  • Primary Citation of Related Structures:  
    2MG4, 4NDL

  • PubMed Abstract: 

    Homodimers are the most common type of protein assembly in nature and have distinct features compared with heterodimers and higher order oligomers. Understanding homodimer interactions at the atomic level is critical both for elucidating their biological mechanisms of action and for accurate modeling of complexes of unknown structure. Computation-based design of novel protein-protein interfaces can serve as a bottom-up method to further our understanding of protein interactions. Previous studies have demonstrated that the de novo design of homodimers can be achieved to atomic-level accuracy by β-strand assembly or through metal-mediated interactions. Here, we report the design and experimental characterization of a α-helix-mediated homodimer with C2 symmetry based on a monomeric Drosophila engrailed homeodomain scaffold. A solution NMR structure shows that the homodimer exhibits parallel helical packing similar to the design model. Because the mutations leading to dimer formation resulted in poor thermostability of the system, design success was facilitated by the introduction of independent thermostabilizing mutations into the scaffold. This two-step design approach, function and stabilization, is likely to be generally applicable, especially if the desired scaffold is of low thermostability.


  • Organizational Affiliation

    Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125;


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Computational designed homodimer
A, B
66Drosophila melanogasterMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 32 
  • Conformers Submitted: 10 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-04-08
    Type: Initial release
  • Version 1.1: 2015-09-02
    Changes: Database references
  • Version 1.2: 2015-09-16
    Changes: Database references
  • Version 1.3: 2023-06-14
    Changes: Data collection, Database references, Other
  • Version 1.4: 2024-05-15
    Changes: Data collection, Database references