Structure of a kinesin-tubulin complex and implications for kinesin motility

The typical function of kinesins is to transport cargo along microtubules. Binding of ATP to microtubule-attached motile kinesins leads to cargo displacement. To better understand the nature of the conformational changes that lead to the power stroke that moves a kinesin's load along a microtubule, we determined the X-ray structure of human kinesin-1 bound to αβ-tubulin. The structure defines the mechanism of microtubule-stimulated ATP hydrolysis, which releases the kinesin motor domain from microtubules. It also reveals the structural linkages that connect the ATP nucleotide to the kinesin neck linker, a 15-amino acid segment C terminal to the catalytic core of the motor domain, to result in the power stroke. ATP binding to the microtubule-bound kinesin favors neck-linker docking. This biases the attachment of kinesin's second head in the direction of the movement, thus initiating each of the steps taken

Insulin-Like Growth Factor-I (IGF-I) Enhances Immune Response in Dexamethasone-Treated or Surgically Stressed Rats Maintained with Total Parenteral Nutrition

Background: New evidence suggests that insulin-like growth factor-I (IGF-I) is an important regulator of immune response. Our objective was to determine the effects of IGF-I on immune response during total parenteral nutrition (TPN) using two stress models. Methods: Male, Sprague-Dawley rats (230 to 250 g) were given TPN with or without coinfusion of recombinant human IGF-I (800 μg/d for 6 days) and subjected to either dexamethasone, a synthetic glucocorticoid, or surgical stress, in the form of a midline abdominal incision. In the dexamethasone model, immune response was assessed by total cellularity of the thymus and spleen, in vitro assays of lymphocyte proliferation, and interleukin 6 (IL-6) production, and concentrations of IL-6 and tumor necrosis factor α (TNF-α) in serum. In the surgical model, flow cytometry was used to identify and quantify splenic populations of T and B lymphocytes and macrophages. Results: In rats immunosuppressed by dexamethasone, IGF-I infusion increased mitogen-induced proliferation of thymocytes, but did not alter cellularity in the thymus; enhanced proliferation and IL-6 production in peripheral blood mononuclear cells following treatment with concanavalin A or lipopolysaccharide; and reduced the serum concentration of IL-6, but not TNF-α. In surgically stressed rats, IGF-I infusion restored the splenic populations of immature and mature B lymphocytes, which were decreased by TPN. Conclusions: Our data demonstrate that IGF-I enhances immune response during TPN in rats. (Journal of Parenteral and Enteral Nutrition 19:444-452, 1995