1LMJ

NMR Study of the Fibrillin-1 cbEGF12-13 Pair of Ca2+ Binding Epidermal Growth Factor-like Domains


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 25 
  • Selection Criteria: structures with acceptable covalent geometry 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Solution Structure and Dynamics of a Calcium Binding Epidermal Growth Factor-like Domain Pair from the Neonatal Region of Human Fibrillin-1.

Smallridge, R.S.Whiteman, P.Werner, J.M.Campbell, I.D.Handford, P.A.Downing, A.K.

(2003) J Biol Chem 278: 12199-12206

  • DOI: https://doi.org/10.1074/jbc.M208266200
  • Primary Citation of Related Structures:  
    1LMJ

  • PubMed Abstract: 

    Fibrillin-1 is a mosaic protein mainly composed of 43 calcium binding epidermal growth factor-like (cbEGF) domains arranged as multiple, tandem repeats. Mutations within the fibrillin-1 gene cause Marfan syndrome (MFS), a heritable disease of connective tissue. More than 60% of MFS-causing mutations identified are localized to cbEGFs, emphasizing that the native properties of these domains are critical for fibrillin-1 function. The cbEGF12-13 domain pair is within the longest run of cbEGFs, and many mutations that cluster in this region are associated with severe, neonatal MFS. The NMR solution structure of Ca(2+)-loaded cbEGF12-13 exhibits a near-linear, rod-like arrangement of domains. This observation supports the hypothesis that all fibrillin-1 (cb)EGF-cbEGF pairs, characterized by a single interdomain linker residue, possess this rod-like structure. The domain arrangement of cbEGF12-13 is stabilized by additional interdomain packing interactions to those observed for cbEGF32-33, which may help to explain the previously reported higher calcium binding affinity of cbEGF13. Based on this structure, a model of cbEGF11-15 that encompasses all known neonatal MFS missense mutations has highlighted a potential binding region. Backbone dynamics data confirm the extended structure of cbEGF12-13 and lend support to the hypothesis that a correlation exists between backbone flexibility and cbEGF domain calcium affinity. These results provide important insight into the potential consequences of MFS-associated mutations for the assembly and biomechanical properties of connective tissue microfibrils.


  • Organizational Affiliation

    Divisions of Structural Biology, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
fibrillin 186Homo sapiensMutation(s): 0 
Gene Names: FBN1
UniProt & NIH Common Fund Data Resources
Find proteins for P35555 (Homo sapiens)
Explore P35555 
Go to UniProtKB:  P35555
PHAROS:  P35555
GTEx:  ENSG00000166147 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP35555
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
CA
Query on CA

Download Ideal Coordinates CCD File 
B [auth A],
C [auth A]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 25 
  • Selection Criteria: structures with acceptable covalent geometry 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2003-04-29
    Type: Initial release
  • Version 1.1: 2008-04-28
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2022-02-23
    Changes: Database references, Derived calculations