Specific sequence motif of 8-Cys repeats of TGF-beta binding proteins, LTBPs, creates a hydrophobic interaction surface for binding of small latent TGF-beta.
Transforming growth factor (TGF)-betas are secreted in large latent complexes consisting of TGF-beta, its N-terminal latency-associated peptide (LAP) propeptide, and latent TGF-beta binding protein (LTBP). LTBPs are required for secretion and subsequent deposition of TGF-beta into the extracellular matrix. TGF-beta1 associates with the 3(rd) 8-Cys repeat of LTBP-1 by LAP. ... All LTBPs, as well as fibrillins, contain multiple 8-Cys repeats. We analyzed the abilities of fibrillins and LTBPs to bind latent TGF-beta by their 8-Cys repeats. 8-Cys repeat was found to interact with TGF-beta1*LAP by direct cysteine bridging. LTBP-1 and LTBP-3 bound efficiently all TGF-beta isoforms, LTBP-4 had a much weaker binding capacity, whereas LTBP-2 as well as fibrillins -1 and -2 were negative. A short, specific TGF-beta binding motif was identified in the TGF-beta binding 8-Cys repeats. Deletion of this motif in the 3(rd) 8-Cys repeat of LTBP-1 resulted in loss of TGF-beta*LAP binding ability, while its inclusion in non-TGF-beta binding 3(rd) 8-Cys repeat of LTBP-2 resulted in TGF-beta binding. Molecular modeling of the 8-Cys repeats revealed a hydrophobic interaction surface and lack of three stabilizing hydrogen bonds introduced by the TGF-beta binding motif necessary for the formation of the TGF-beta*LAP - 8-Cys repeat complex inside the cells.
Mesh Terms:
Amino Acid Motifs, Amino Acid Sequence, Carrier Proteins, Cysteine, Epithelial Cells, Fibroblasts, Humans, Intracellular Signaling Peptides and Proteins, Latent TGF-beta Binding Proteins, Microfilament Proteins, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Isoforms, Protein Structure, Tertiary, Recombinant Fusion Proteins, Sequence Alignment, Transfection, Transforming Growth Factor beta
Amino Acid Motifs, Amino Acid Sequence, Carrier Proteins, Cysteine, Epithelial Cells, Fibroblasts, Humans, Intracellular Signaling Peptides and Proteins, Latent TGF-beta Binding Proteins, Microfilament Proteins, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Isoforms, Protein Structure, Tertiary, Recombinant Fusion Proteins, Sequence Alignment, Transfection, Transforming Growth Factor beta
Mol. Biol. Cell
Date: Aug. 01, 2000
PubMed ID: 10930463
View in: Pubmed Google Scholar
Download Curated Data For This Publication
4788
Switch View:
- Interactions 2