@article {2653,
	title = {Helix Straightening as an Activation Mechanism in the Gelsolin Superfamily of Actin Regulatory Proteins},
	journal = {Journal of Biological Chemistry},
	volume = {284},
	number = {32},
	year = {2009},
	note = {ISI Document Delivery No.: 478CCTimes Cited: 4Cited Reference Count: 23Wang, Hui Chumnarnsilpa, Sakesit Loonchanta, Anantasak Li, Qiang Kuan, Yang-Mei Robine, Sylvie Larsson, Marten Mihalek, Ivana Burtnick, Leslie D. Robinson, Robert C.},
	month = {Aug},
	pages = {21265-21269},
	type = {Article},
	abstract = {Villin and gelsolin consist of six homologous domains of the gelsolin/cofilin fold (V1-V6 and G1-G6, respectively). Villin differs from gelsolin in possessing at its C terminus an unrelated seventh domain, the villin headpiece. Here, we present the crystal structure of villin domain V6 in an environment in which intact villin would be inactive, in the absence of bound Ca2+ or phosphorylation. The structure of V6 more closely resembles that of the activated form of G6, which contains one bound Ca2+, rather than that of the calcium ion-free form of G6 within intact inactive gelsolin. Strikingly apparent is that the long helix in V6 is straight, as found in the activated form of G6, as opposed to the kinked version in inactive gelsolin. Molecular dynamics calculations suggest that the preferable conformation for this helix in the isolated G6 domain is also straight in the absence of Ca2+ and other gelsolin domains. However, the G6 helix bends in intact calcium ion-free gelsolin to allow interaction with G2 and G4. We suggest that a similar situation exists in villin. Within the intact protein, a bent V6 helix, when triggered by Ca2+, straightens and helps push apart adjacent domains to expose actin-binding sites within the protein. The sixth domain in this superfamily of proteins serves as a keystone that locks together a compact ensemble of domains in an inactive state. Perturbing the keystone initiates reorganization of the structure to reveal previously buried actin-binding sites.},
	keywords = {BINDING PROTEINS, calcium, COMPLEX, DOMAINS, F-ACTIN, HEADPIECE, SITES, SWITCH, TERMINAL HALF, VILLIN},
	isbn = {0021-9258},
	url = {<Go to ISI>://000268564400020},
	author = {Wang, H. and Chumnarnsilpa, S. and Loonchanta, A. and Li, Q. and Kuan, Y. M. and Robine, S. and Larsson, M. and Mihalek, I. and Burtnick, L. D. and Robinson, R. C.}
}
@article {5199,
	title = {Structure of Cdc4p, a contractile ring protein essential for cytokinesis in Schizosaccharomyces pombe},
	journal = {Journal of Biological Chemistry},
	volume = {276},
	number = {8},
	year = {2001},
	note = {ISI Document Delivery No.: 404RUTimes Cited: 16Cited Reference Count: 49},
	month = {Feb},
	pages = {5943-5951},
	type = {Article},
	abstract = {The Schizosaccharomyces pombe Cdc4 protein is required for the formation and function of the contractile ring, presumably acting as a myosin light chain. By using NMR spectroscopy, we demonstrate that purified Cdc4p is a monomeric protein with two structurally independent domains, each exhibiting a fold reminiscent of the EF-hand class of calcium-binding proteins. Although Cdc4p has one potentially functional calcium-binding site, it does not bind calcium in vitro. Three variants of Cdc4p containing single point mutations responsible for temperature-sensitive arrest of the cell cycle at cytokinesis (Gly-19 to Glu, Gly-82 to Asp, and Gly-107 to Ser) were also characterized by NMR and circular dichroism spectroscopy. In each case, the amino acid substitution only leads to small perturbations in the conformation of the protein. Furthermore, thermal unfolding studies indicate that, like wild-type Cdc4p, the three mutant forms are all extremely stable, remaining completely folded at temperatures significantly above those causing failure of cytokinesis in intact cells. Therefore, the altered phenotype must arise directly from a disruption of the function of Cdc4p rather than indirectly through a disruption of its overall structure. Several mutant alleles of Cdc4p also show interallelic complementation in diploid cells. This phenomenon can be explained if Cdcp4 has more than one essential function or, alternatively, if two mutant proteins assemble to form a functional complex. Based on the structure of Cdc4p, possible models for interallelic complementation including interactions with partner proteins and the formation of a myosin complex with Cdc4p fulfilling the role of both an essential and regulatory light chain are proposed.},
	keywords = {BINDING PROTEINS, CALCIUM-SATURATED STATES, ESSENTIAL LIGHT-CHAIN, FISSION YEAST, MYOSIN HEAVY-CHAIN, NUCLEAR-MAGNETIC-RESONANCE, REGULATORY DOMAIN, SCALLOP MYOSIN, TARGETED DISRUPTION, TROPONIN-C},
	isbn = {0021-9258},
	url = {<Go to ISI>://000167115100072},
	author = {Slupsky, C. M. and Desautels, M. and Huebert, T. and Zhao, R. H. and Hemmingsen, S. M. and McIntosh, L. P.}
}
