@article {2546,
	title = {Ca2+ binding by domain 2 plays a critical role in the activation and stabilization of gelsolin},
	journal = {Proceedings of the National Academy of Sciences of the United States of America},
	volume = {106},
	number = {33},
	year = {2009},
	note = {ISI Document Delivery No.: 484WETimes Cited: 5Cited Reference Count: 30Nag, Shalini Ma, Qing Wang, Hui Chumnarnsilpa, Sakesit Lee, Wei Lin Larsson, Marten Kannan, Balakrishnan Hernandez-Valladarez, Maria Burtnick, Leslie D. Robinson, Robert C.},
	month = {Aug},
	pages = {13713-13718},
	type = {Article},
	abstract = {Gelsolin consists of six homologous domains (G1-G6), each containing a conserved Ca-binding site. Occupation of a subset of these sites enables gelsolin to sever and cap actin filaments in a Ca-dependent manner. Here, we present the structures of Ca-free human gelsolin and of Ca-bound human G1-G3 in a complex with actin. These structures closely resemble those determined previously for equine gelsolin. However, the G2 Ca-binding site is occupied in the human G1-G3/actin structure, whereas it is vacant in the equine version. In-depth comparison of the Ca-free and Ca-activated, actin-bound human gelsolin structures suggests G2 and G6 to be cooperative in binding Ca2+ and responsible for opening the G2-G6 latch to expose the F-actin-binding site on G2. Mutational analysis of the G2 and G6 Ca-binding sites demonstrates their interdependence in maintaining the compact structure in the absence of calcium. Examination of Ca binding by G2 in human G1-G3/actin reveals that the Ca2+ locks the G2-G3 interface. Thermal denaturation studies of G2-G3 indicate that Ca binding stabilizes this fragment, driving it into the active conformation. The G2 Ca-binding site is mutated in gelsolin from familial amyloidosis (Finnish-type) patients. This disease initially proceeds through protease cleavage of G2, ultimately to produce a fragment that forms amyloid fibrils. The data presented here support a mechanism whereby the loss of Ca binding by G2 prolongs the lifetime of partially activated, intermediate conformations in which the protease cleavage site is exposed.},
	keywords = {actin, AMYLOIDOGENESIS, biosynthesis, calcium, calcium activated, calcium dependent, FAMILIAL AMYLOIDOSIS, IDENTIFICATION, PLASMA GELSOLIN, PROTEIN, SITE, TERMINAL HALF, TIRF},
	isbn = {0027-8424},
	url = {<Go to ISI>://000269078700018},
	author = {Nag, S. and Ma, Q. and Wang, H. and Chumnarnsilpa, S. and Lee, W. L. and Larsson, M. and Kannan, B. and Hernandez-Valladarez, M. and Burtnick, L. D. and Robinson, R. C.}
}
@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 {1612,
	title = {The structure of gelsolin bound to ATP},
	journal = {Journal of Molecular Biology},
	volume = {357},
	number = {3},
	year = {2006},
	note = {ISI Document Delivery No.: 030IYTimes Cited: 7Cited Reference Count: 28},
	month = {Mar},
	pages = {765-772},
	type = {Article},
	abstract = {Calcium activation of the actin-modifying properties of gelsolin is sensitive to ATP. Here, we show that soaking calcium-free gelsolin crystals in ATP-containing media results in ATP occupying a site that spans the two pseudosymmetrical halves of the protein. ATP binding involves numerous polar and hydrophobic contacts and is identical for the two copies of gelsolin related by non-crystallographic symmetry within the crystal. The gamma-phosphate of ATP participates in several charge-charge interactions consistent with the preference of gelsolin for ATP, as a binding partner, over ADP. In addition, disruption of the ATP-binding site through Ca2+ activation of gelsolin reveals why ATP binds more tightly to the inactive molecule, and suggests how the binding of ATP may modulate the sensitivity of gelsolin to calcium ions. Similarities between the ATP and PIP2 interactions with the C-terminal half of gelsolin are evident from their overlapping binding sites and in that both molecules bind more tightly in the absence of calcium ions. We propose a model for how PIP2 may bind to calcium-free gelsolin based on the ATP-binding site. (c) 2006 Elsevier Ltd. All rights reserved.},
	keywords = {5-BISPHOSPHATE, actin, ATP, BINDING-SITE, calcium, CRYSTAL-STRUCTURE, DOMAIN, gelsolin, HUMAN-PLASMA GELSOLIN, IDENTIFICATION, PHOSPHATIDYLINOSITOL 4, PIP2, PROTEIN, TERMINAL HALF},
	isbn = {0022-2836},
	url = {<Go to ISI>://000236629300007},
	author = {Urosev, D. and Ma, Q. and Tan, A. L. C. and Robinson, R. C. and Burtnick, L. D.}
}
