Cyclase-associated protein

Stabilizer of iron transporter SufD Cyclase-associated protein... 

Dodatko, T., Fedorov, A. A., Grynberg, M., Patskovsky, Y., Rozwarski, D. A., Jaroszewski, L., Aronoff-Spencer, E., Kondraskina, E., Irving, T., Godzik, A., and Almo, S. C. (2004). Crystal structure of the actin binding domain of the cyclase-associated protein. Biochemistry 43, 10628-10641. 

C terminus (ILWEQ), WASp homology 2 (WH2), profilin (PROF), and cyclase-associated protein, domains are all present in fungi, plants, and metazoa. Many of these domains bind similar sites on actin, although they possess different properties with respect to actin polymerization (reviewed in Van Troys et al., 1999). 

BertlingE, Hotulainen P, A ttila PK et al. Cyclase-associated protein 1 (CAPl) promotes cofilin-induced actin dynamics in mammalian nonmusclc cells. Mol Biol Cell 2004 15(5) 2324-2334. 

Nishiguchi, K.M., Sokal, I., Yang, L., Roychowdhury, N., Palczewski, K., Berson, E.L., Dryja, T.P., and Baehr, W. (2004). A Novel Mutation (1143NT) in Guanylate Cyclase-Activating Protein 1 (GCAP1) Associated with Autosomal Dominant Cone Degeneration. Invest Ophthalmol. Vis. Sci 45 3863-3870. 

The hormonal stimulation of adenylyl cyclase is effected by a transmembrane signaling pathway consisting of three components, all membrane-associated. Binding of hormone to the external surface of a hormone receptor causes a conformational change in this transmembrane protein, which in turn stimulates a GTP-binding protein (abbreviated G protein). G proteins are heterotrimeric proteins consisting of a- (45-47 kD), /3- (35 kD), and y- (7-9 kD) subunits. The a-subunit binds GDP or GTP and has an intrinsic, slow... 

FIGURE 15.21 Hormone (H) binding to its receptor (R) creates a hormone receptor complex (H R) that catalyzes GDP-GTP exchange on the o -subunit of the heterotrimer G protein (G ), replacing GDP with GTP. The G -subunit with GTP bound dissociates from the /37-subunits and binds to adenylyl cyclase (AC). AC becomes active upon association with G GTP and catalyzes the formation of cAMP from ATP. With time, the intrinsic GTPase activity of the G -subunit hydrolyzes the bound GTP, forming GDP this leads to dissociation of G GDP from AC, reassociation of G with the /Sy subunits, and cessation of AC activity. AC and the hormone receptor H are integral plasma membrane proteins G and G are membrane-anchored proteins. 

Stimulation and inhibition of the enzyme by the GPCR-G-protein cycle occur by analogous mechanisms. Agonists induce hormone receptors to increase a Ga-GDP-GTP exchange and subsequent Ga 3y dissociation (GDP-a py + GTP GTP-ax + [3y + GDP) (Fig. 4). Consequently, agents that affect either the dissociation of either G or Gs, or the association of their respective as, a , or (3y subunits with adenylyl cyclase could affect rates of cAMP formation in enzyme preparations or in intact cells and tissues. There are several important examples. Gas is stably activated by poorly hydrolyzable analogs of GTP, e.g. GTPyS... 

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