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Neuropilin (Nrp) is a cell surface receptor with essential roles in angiogenesis and axon guidance. Interactions between Nrp and the positively charged C termini of its ligands, VEGF and semaphorin, are mediated by Nrp domains b1 and b2, which share homology to coagulation factor domains. We report here the crystal structure of the tandem b1 and b2 domains of Nrp-1 (N1b1b2) and show that they form a single structural unit. Cocrystallization of N1b1b2 with Tuftsin, a peptide mimic of the VEGF C terminus, reveals the site of interaction with the basic tail of VEGF on the b1 domain. We also show that heparin promotes N1b1b2 dimerization and map the heparin binding site on N1b1b2. These results provide a detailed picture of interactions at the core of the Nrp signaling complex and establish a molecular basis for the synergistic effects of heparin on Nrp-mediated signaling. semaphorin | Tuftsin | VEGF

The bacterial blue-light photoactive yellow protein, upon illumination with 7 nanoseconds laser pulse, exhibits structural perturbations at the chromophore, which spreads throughout the protein the 'protein quake' with its 'epicenter' residing in the carbonyl moiety of the chromophore.

BPAG1, a 230 kDa protein, is found to be present in the inner plates of the hemidesmosomes, which are specialized integrin-mediated adherens junctions. BPAG1 acts as an anchor for intermediate filaments at the base of the epidermal cells. In absence of BPAG1, there is loss of cell migration and the hemidesmosomes become extremely fragile, lacking an inner plate and attached cytoskeleton. Mechanical integrity is also affected. No loss of cell adhesion or cell growth is seen in mice lacking the BPAG1 gene, but these mice exhibit symptoms of dystonia musculorum (dt/dt mice) in which there is a dystonia accompanied by sensory nerve degeneration.

Studies the photocycle of the bacterial blue-light photoreceptor, photoactive yellow protein from nanoseconds to seconds via a molecular movie at 1.8 angstrom. Difference electron density maps relative to the dark state; Identification of the step critical to entry into the photocycle; Propagation of the structural perturbation generated at the chromophore.