2ROC

Solution structure of Mcl-1 Complexed with Puma


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 256 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the least restraint violations 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structure of the BH3 Domains from the p53-Inducible BH3-Only Proteins Noxa and Puma in Complex with Mcl-1

Day, C.L.Smits, C.Fan, F.C.Lee, E.F.Fairlie, W.D.Hinds, M.G.

(2008) J Mol Biol 380: 958-971

  • DOI: https://doi.org/10.1016/j.jmb.2008.05.071
  • Primary Citation of Related Structures:  
    2ROC, 2ROD

  • PubMed Abstract: 

    Pro-survival proteins in the B-cell lymphoma-2 (Bcl-2) family have a defined specificity profile for their cell death-inducing BH3-only antagonists. Solution structures of myeloid cell leukaemia-1 (Mcl-1) in complex with the BH3 domains from Noxa and Puma, two proteins regulated by the tumour suppressor p53, show that they bind as amphipathic alpha-helices in the same hydrophobic groove of Mcl-1, using conserved residues for binding. Thermodynamic parameters for the interaction of Noxa, Puma and the related BH3 domains of Bmf, Bim, Bid and Bak with Mcl-1 were determined by calorimetry. These unstructured BH3 domains bind Mcl-1 with affinities that span 3 orders of magnitude, and binding is an enthalpically driven and entropy-enthalpy-compensated process. Alanine scanning analysis of Noxa demonstrated that only a subset of residues is required for interaction with Mcl-1, and these residues are localised to a short highly conserved sequence motif that defines the BH3 domain. Chemical shift mapping of Mcl-1:BH3 complexes showed that Mcl-1 engages all BH3 ligands in a similar way and that, in addition to changes in the immediate vicinity of the binding site, small molecule-wide structural adjustments accommodate ligand binding. Our studies show that unstructured peptides, such as the BH3 domains, behave like their structured counterparts and can bind tightly and selectively in an enthalpically driven process.


  • Organizational Affiliation

    Department of Biochemistry, University of Otago, Dunedin 9054, New Zealand.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Induced myeloid leukemia cell differentiation protein Mcl-1 homolog162Mus musculusMutation(s): 0 
Gene Names: Mcl-1
UniProt & NIH Common Fund Data Resources
Find proteins for P97287 (Mus musculus)
Explore P97287 
Go to UniProtKB:  P97287
IMPC:  MGI:101769
Entity Groups  
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UniProt GroupP97287
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Bcl-2-binding component 327Mus musculusMutation(s): 1 
Gene Names: Puma
UniProt & NIH Common Fund Data Resources
Find proteins for Q99ML1 (Mus musculus)
Explore Q99ML1 
Go to UniProtKB:  Q99ML1
IMPC:  MGI:2181667
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ99ML1
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 256 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the least restraint violations 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-07-08
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2021-11-10
    Changes: Data collection, Database references, Derived calculations