Document Detail

Solution structure of the transforming growth factor beta-binding protein-like module, a domain associated with matrix fibrils.
MedLine Citation:
PMID:  9362480     Owner:  NLM     Status:  MEDLINE    
Here we describe the high resolution nuclear magnetic resonance (NMR) structure of a transforming growth factor beta (TGF-beta)-binding protein-like (TB) domain, which comes from human fibrillin-1, the protein defective in the Marfan syndrome (MFS). This domain is found in fibrillins and latent TGF-beta-binding proteins (LTBPs) which are localized to fibrillar structures in the extracellular matrix. The TB domain manifests a novel fold which is globular and comprises six antiparallel beta-strands and two alpha-helices. An unusual cysteine triplet conserved in the sequences of TB domains is localized to the hydrophobic core, at the C-terminus of an alpha-helix. The structure is stabilized by four disulfide bonds which pair in a 1-3, 2-6, 4-7, 5-8 pattern, two of which are solvent exposed. Analyses of MFS-causing mutations and the fibrillin-1 cell-binding RGD site provide the first clues to the surface specificity of TB domain interactions. Modelling of a homologous TB domain from LTBP-1 (residues 1018-1080) suggests that hydrophobic contacts may play a role in its interaction with the TGF-beta1 latency-associated peptide.
X Yuan; A K Downing; V Knott; P A Handford
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The EMBO journal     Volume:  16     ISSN:  0261-4189     ISO Abbreviation:  EMBO J.     Publication Date:  1997 Nov 
Date Detail:
Created Date:  1998-01-05     Completed Date:  1998-01-05     Revised Date:  2010-09-13    
Medline Journal Info:
Nlm Unique ID:  8208664     Medline TA:  EMBO J     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  6659-66     Citation Subset:  IM    
Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
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MeSH Terms
Amino Acid Sequence
Cell Adhesion
Extracellular Matrix*
Marfan Syndrome
Microfilament Proteins / chemistry*
Models, Molecular
Molecular Sequence Data
Nuclear Magnetic Resonance, Biomolecular
Peptide Fragments / chemistry*
Protein Structure, Secondary
Protein Structure, Tertiary
Recombinant Proteins / chemistry
Sequence Homology, Amino Acid
Transforming Growth Factor beta*
Grant Support
//Wellcome Trust
Reg. No./Substance:
0/Microfilament Proteins; 0/Peptide Fragments; 0/Recombinant Proteins; 0/Solutions; 0/Transforming Growth Factor beta; 0/fibrillin

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