@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 {813,
	title = {Structure of the N-terminal half of gelsolin bound to actin: roles in severing, apoptosis and FAF},
	journal = {Embo Journal},
	volume = {23},
	number = {14},
	year = {2004},
	note = {ISI Document Delivery No.: 847NBTimes Cited: 41Cited Reference Count: 59},
	month = {Jul},
	pages = {2713-2722},
	type = {Article},
	abstract = {The actin filament-severing functionality of gelsolin resides in its N-terminal three domains (G1 - G3). We have determined the structure of this fragment in complex with an actin monomer. The structure reveals the dramatic domain rearrangements that activate G1 - G3, which include the replacement of interdomain interactions observed in the inactive, calcium-free protein by new contacts to actin, and by a novel G2 - G3 interface. Together, these conformational changes are critical for actin filament severing, and we suggest that their absence leads to the disease Finnish-type familial amyloidosis. Furthermore, we propose that association with actin drives the calcium-independent activation of isolated G1 G3 during apoptosis, and that a similar mechanism operates to activate native gelsolin at micromolar levels of calcium. This is the first structure of a filament-binding protein bound to actin and it sets stringent, high-resolution limitations on the arrangement of actin protomers within the filament.},
	keywords = {5-BISPHOSPHATE, actin, AMYLOIDOSIS-FINNISH TYPE, apoptosis, BINDING-SITE, CA2+ REGULATION, calcium, CRYSTAL-STRUCTURE, crystallographic structure, F-ACTIN, FAMILIAL AMYLOIDOSIS, FILAMENT BARBED ENDS, gelsolin, PHOSPHATIDYLINOSITOL 4, PLASMA GELSOLIN, X-RAY},
	isbn = {0261-4189},
	url = {<Go to ISI>://000223398800002},
	author = {Burtnick, L. D. and Urosev, D. and Irobi, E. and Narayan, K. and Robinson, R. C.}
}
@article {348,
	title = {The calcium activation of gelsolin: Insights from the 3 angstrom structure of the G4-G6/actin complex},
	journal = {Journal of Molecular Biology},
	volume = {324},
	number = {4},
	year = {2002},
	note = {ISI Document Delivery No.: 625PRTimes Cited: 48Cited Reference Count: 32},
	month = {Dec},
	pages = {691-702},
	type = {Article},
	abstract = {Gelsolin participates in the reorganization of the actin cytoskeleton that is required during such phenomena as cell movement, cytokinesis, and apoptosis. It consists of six structurally similar domains, G1-G6, which are arranged at resting intracellular levels of calcium ion so as to obscure the three actin-binding surfaces. Elevation of Ca2+ concentrations releases latches within the constrained structure and produces large shifts in the relative positioning of the domains, permitting gelsolin to bind to and sever actin filaments. How Ca2+ is able to activate gelsolin has been a major question concerning the function of this protein. We present the improved structure of the C-terminal half of gelsolin bound to monomeric actin at 3.0 Angstrom resolution. Two classes of Ca2+-binding site are evident on gelsolin: type 1 sites share coordination of Ca2+ with actin, while type 2 sites are wholly contained within gelsolin. This structure of the complex reveals the locations of two novel metal ion-binding sites in domains G5 and G6, respectively. We identify both as type 2 sites. The absolute conservation of the type 2 calcium-ligating residues across the six,domains of gelsolin suggests that this site exists in each of the domains. In total, gelsolin has the potential to bind eight calcium ions, two type 1 and six type 2. The function of the type 2 sites is to facilitate structural rearrangements within gelsolin as part of the activation and actin-binding and severing processes. We propose the novel type 2 site in G6 to be the critical site that initiates overall activation of gelsolin by releasing the tail latch that locks calcium-free gelsolin in a conformation unable to bind actin. (C) 2002 Elsevier Science Ltd. All rights reserved.},
	keywords = {actin, ACTIVATION, ACTOPHORIN, BINDING DOMAIN, CA2+, calcium, CAPPING PROTEIN, F-ACTIN, FAMILIAL AMYLOIDOSIS, FINNISH TYPE, gelsolin, IDENTIFICATION, MECHANISM, PLASMA GELSOLIN, REGULATION, severing},
	isbn = {0022-2836},
	url = {<Go to ISI>://000179825300011},
	author = {Choe, H. and Burtnick, L. D. and Mejillano, M. and Yin, H. L. and Robinson, R. C. and Choe, S.}
}
