Sacha A. Jensen

Learn More
The Notch receptor and its ligands are key components in a core metazoan signaling pathway that regulates the spatial patterning, timing and outcome of many cell-fate decisions. Ligands contain a disulfide-rich Delta/Serrate/LAG-2 (DSL) domain required for Notch trans-activation or cis-inhibition. Here we report the X-ray structure of a receptor binding(More)
Fibrillins and LTBPs [latent TGFβ (transforming growth factor β)-binding proteins] perform vital and complex roles in the extracellular matrix and are relevant to a wide range of human diseases. These proteins share a signature 'eight cysteine' or 'TB (TGFβ-binding protein-like)' domain that is found nowhere else in the human proteome, and which has been(More)
Elastic fibers consist primarily of an amorphous elastin core associated with microfibrils, 10-12 nm in diameter, containing fibrillins and microfibril-associated glycoproteins (MAGPs). To investigate the interaction of MAGP-1 with tropoelastin and fibrillin-1, we expressed human MAGP-1 as a T7-tag fusion protein in Escherichia coli. Refolding of the(More)
Human fibrillin-1 is the major structural protein of extracellular matrix 10-12 nm microfibrils. It has a disulfide-rich modular organization which consists primarily of cbEGF (Ca(2+)-binding epidermal growth factor-like) domains and TB (transforming growth factor beta-binding protein-like) domains. TB4 contains an RGD (Arg-Gly-Asp) integrin-binding motif.(More)
Force-bearing tissues such as blood vessels, lungs, and ligaments depend on the properties of elasticity and flexibility. The 10 to 12 nm diameter fibrillin microfibrils play vital roles in maintaining the structural integrity of these highly dynamic tissues and in regulating extracellular growth factors. In humans, defective microfibril function results in(More)
The fibrillins and latent transforming growth factor-beta binding proteins (LTBPs) form a superfamily of structurally-related proteins consisting of calcium-binding epidermal growth factor-like (cbEGF) domains interspersed with 8-cysteine-containing transforming growth factor beta-binding protein-like (TB) and hybrid (hyb) domains. Fibrillins are the major(More)
Tropoelastin is the soluble precursor of elastin, the major component of the extracellular elastic fiber. Tropoelastin undergoes self-association via an inverse temperature transition termed coacervation, which is a crucial step in elastogenesis. Coacervation of tropoelastin takes place through multiple intermolecular interactions of its hydrophobic(More)
The temperature-dependent association of tropoelastin molecules through coacervation is an essential step in their assembly leading to elastogenesis. The relative contributions of C-terminal hydrophobic domains in coacervation were assessed. Truncated tropoelastins were constructed with N termini positioned variably downstream of domain 25. The purified(More)
FBLN5 encodes fibulin-5, an extracellular matrix calcium-binding glycoprotein that is essential for elastic fibre formation. FBLN5 mutations are associated with two distinct human diseases, age-related macular degeneration (AMD) and cutis laxa (CL), but the biochemical basis for the pathogenic effects of these mutations is poorly understood. Two missense(More)
Coacervation of soluble tropoelastin molecules is characterized by thermodynamically reversible association as temperature is increased under appropriately juxtaposed ionic conditions, protein concentration and pH. Coacervation plays a critical role in the assembly of these elastin precursors in elastic fiber formation. To examine the effect of(More)