3KMP

Crystal Structure of SMAD1-MH1/DNA complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.250 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.208 

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This is version 1.3 of the entry. See complete history


Literature

Structure of Smad1 MH1/DNA complex reveals distinctive rearrangements of BMP and TGF-beta effectors.

BabuRajendran, N.Palasingam, P.Narasimhan, K.Sun, W.Prabhakar, S.Jauch, R.Kolatkar, P.R.

(2010) Nucleic Acids Res 38: 3477-3488

  • DOI: https://doi.org/10.1093/nar/gkq046
  • Primary Citation of Related Structures:  
    3KMP

  • PubMed Abstract: 

    Smad1 is a downstream effector of the BMP signaling pathway that binds regulatory DNA to execute gene expression programs leading to, for example, the maintenance of pluripotency in mice. On the contrary, the TGF-beta-activated Smad3 triggers strikingly different programs such as mesodermal differentiation in early development. Because Smad1 and Smad3 contain identical amino acids at the DNA contact interface it is unclear how they elicit distinctive bioactivities. Here, we report the crystal structure of the MH1 domain of Smad1 bound to a palindromic Smad binding element. Surprisingly, the DNA contact interface of Smad1 is drastically rearranged when compared to Smad3. The N-terminal helix 1 of Smad1 is dislodged from its intramolecular binding site and adopts a domain swapped arrangement with a symmetry-related molecule. As a consequence, helix 2 kinks away from the double helix disabling several key phosphate backbone interactions. Thermal melting analysis corroborates a decompacted conformation of Smad1 and DNA binding assays indicate a lower overall affinity of Smad1 to DNA but increased cooperativity when binding to palindromic DNA motifs. These findings suggest that Smad1 and Smad3 evolved differential qualities to assemble on composite DNA elements and to engage in co-factor interactions by remodeling their N-termini.


  • Organizational Affiliation

    Laboratory of Structural Biochemistry, Genome Institute of Singapore, 60 Biopolis Street, Singapore.


Macromolecules

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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
SMAD1-MH1
A, B
124Mus musculusMutation(s): 0 
Gene Names: Smad1
UniProt
Find proteins for P70340 (Mus musculus)
Explore P70340 
Go to UniProtKB:  P70340
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP70340
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains LengthOrganismImage
5'-D(P*AP*TP*CP*AP*GP*TP*CP*TP*AP*GP*AP*CP*AP*TP*A)-3'15N/A
Sequence Annotations
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  • Reference Sequence

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Entity ID: 3
MoleculeChains LengthOrganismImage
5'-D(P*GP*TP*AP*TP*GP*TP*CP*TP*AP*GP*AP*CP*TP*GP*A)-3'15N/A
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.250 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.208 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 73.938α = 90
b = 77.49β = 90
c = 83.78γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
PDB_EXTRACTdata extraction

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-02-23
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2013-12-11
    Changes: Database references
  • Version 1.3: 2024-03-20
    Changes: Data collection, Database references, Derived calculations, Refinement description