Publications (109) View all
-
Article: (1)H, (13)C and (15)N resonance assignments for the fibrillin-1 EGF2-EGF3-hybrid1-cbEGF1 four-domain fragment.
[show abstract] [hide abstract]
ABSTRACT: Fibrillins are large extracellular glycoproteins that form the principal component of microfibrils. These perform a vital structural function in the extracellular matrix of many tissues. Fibrillins have also been implicated in mediating a number of protein-protein interactions, some of which may be significant in regulating growth factors such as transforming growth factor β. Here we present the backbone and side-chain (1)H, (13)C and (15)N assignments for a 19 kDa protein fragment derived from the N-terminus of human fibrillin-1, encompassing four domains in total. These domains include the second and third epidermal growth factor-like (EGF) domains, the first hybrid domain (hyb1), and the first calcium-binding EGF domain of fibrillin-1. This region of fibrillin-1 is of particular interest as the hyb1 domain has been suggested to play a role in microfibril assembly, as well as several other protein-protein interactions.Biomolecular NMR Assignments 05/2013; · 0.72 Impact Factor -
Article: Backbone (1)H, (13)C and (15)N resonance assignment of the C-terminal EGF-cbEGF pair of LTBP1 and flanking residues.
[show abstract] [hide abstract]
ABSTRACT: Latent TGFβ binding protein 1 (LTBP1) is a large extracellular protein that has been shown to bind covalently to the propeptide of TGFβ cytokines and form a large latent complex, which is then incapable of binding TGFβ receptors. LTBP1 has also been demonstrated to interact with a number of insoluble extracellular matrix components, such as fibrillin, which may play a role in TGFβ regulation. Here we present the backbone (1)H, (13)C and (15)N assignments for two EGF domains of human LTBP1, and flanking regions, together forming a 12 kDa protein fragment at the C-terminus of LTBP1. This region is of particular interest as it is postulated to be involved in interactions with fibrillin microfibrils.Biomolecular NMR Assignments 03/2013; · 0.72 Impact Factor -
Article: Molecular basis for Jagged-1/Serrate recognition by Notch.
[show abstract] [hide abstract]
ABSTRACT: We have mapped a Jagged/Serrate binding site to specific residues within the 12th EGF domain of human and Drosophila Notch. Two critical residues, involved in a hydrophobic interaction, provide a ligand-binding platform and are adjacent to a Fringe -sensitive residue which modulates Notch activity. Our data suggest that small variations within the binding site fine tune ligand specificity, which may explain the observed sequence heterogeneity in mammalian Notch paralogues, and should allow the development of paralogue-specific ligand-blocking antibodies. As a proof of principle, we have generated a Notch-1 specific monoclonal antibody that blocks binding, thus paving the way for antibody tools for research and therapeutic applications.Journal of Biological Chemistry 01/2013; · 4.77 Impact Factor -
Article: (1)H, (13)C and (15)N assignments of the four N-terminal domains of human fibrillin-1.
[show abstract] [hide abstract]
ABSTRACT: Fibrillins are extracellular, disulphide-rich glycoproteins that form 10-12 nm diameter microfibrils in connective tissues. They are found in the majority of higher animals, from jellyfish to humans. Fibrillin microfibrils confer properties of elasticity and strength on connective tissue and regulate growth factor availability in the extracellular matrix (ECM). Mutations in FBN1, the human gene encoding the fibrillin-1 isoform, are linked to several inherited connective tissue disorders. The fibrillin-1 N-terminus forms many functionally-important interactions, both with other fibrillin molecules and various ECM components. In particular, the first four domains, the fibrillin unique N-terminal (FUN) and three epidermal growth factor (EGF)-like domains (FUN-EGF3), are implicated in microfibril assembly and growth factor sequestration. The structure of these domains, which comprise 134 residues, is unknown. We have produced a recombinant fragment corresponding to this region of human fibrillin-1. Here, we report (1)H, (13)C and (15)N resonance assignments of the FUN-EGF3 fragment. Assignments will facilitate structure determination, analysis of interdomain dynamics and the mapping of interaction surfaces.Biomolecular NMR Assignments 12/2012; · 0.72 Impact Factor -
Article: (1)H, (13)C and (15)N resonance assignments for the oxidized and reduced states of the N-terminal domain of DsbD from Escherichia coli.
[show abstract] [hide abstract]
ABSTRACT: Viability and pathogenicity of Gram-negative bacteria is linked to the cytochrome c maturation and the oxidative protein folding systems in the periplasm. The transmembrane reductant conductor DsbD is a unique protein which provides the necessary reducing power to both systems through thiol-disulfide exchange reactions in a complex network of protein-protein interactions. The N-terminal domain of DsbD (nDsbD) is the delivery point of the reducing power originating from cytoplasmic thioredoxin to a variety of periplasmic partners. Here we report (1)H, (13)C and (15)N assignments for resonances of nDsbD in its oxidized and reduced states. These assignments provide the starting point for detailed investigations of the interactions of nDsbD with its protein partners.Biomolecular NMR Assignments 11/2011; 6(2):163-7. · 0.72 Impact Factor
