This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1apj
From Proteopedia
| Line 7: | Line 7: | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1apj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1apj OCA], [http://www.ebi.ac.uk/pdbsum/1apj PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1apj RCSB]</span> | ||
}} | }} | ||
| Line 14: | Line 17: | ||
==Overview== | ==Overview== | ||
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. | 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. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Aortic aneurysm, ascending, and dissection OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134797 134797]], Ectopia lentis, familial OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134797 134797]], MASS syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134797 134797]], Marfan syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134797 134797]], Shprintzen-Goldberg syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134797 134797]], Weill-Marchesani syndrome, dominant OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134797 134797]] | ||
==About this Structure== | ==About this Structure== | ||
| Line 37: | Line 37: | ||
[[Category: tb module]] | [[Category: tb module]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 18:45:00 2008'' |
Revision as of 15:45, 30 March 2008
| |||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
NMR STUDY OF THE TRANSFORMING GROWTH FACTOR BETA BINDING PROTEIN-LIKE DOMAIN (TB MODULE/8-CYS DOMAIN), NMR, 21 STRUCTURES
Overview
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.
About this Structure
1APJ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Solution structure of the transforming growth factor beta-binding protein-like module, a domain associated with matrix fibrils., Yuan X, Downing AK, Knott V, Handford PA, EMBO J. 1997 Nov 17;16(22):6659-66. PMID:9362480
Page seeded by OCA on Sun Mar 30 18:45:00 2008
