@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 {2395,
	title = {The crystal structure of the C-terminus of adseverin reveals the actin-binding interface},
	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: 0Cited Reference Count: 21Chumnarnsilpa, Sakesit Lee, Wei Lin Nag, Shalini Kannan, Balakrishnan Larsson, Marten Burtnick, Leslie D. Robinson, Robert C.},
	month = {Aug},
	pages = {13719-13724},
	type = {Article},
	abstract = {Adseverin is a member of the calcium-regulated gelsolin superfamily of actin severing and capping proteins. Adseverin comprises 6 homologous domains (A1-A6), which share 60\% identity with the 6 domains from gelsolin (G1-G6). Adseverin is truncated in comparison to gelsolin, lacking the C-terminal extension that masks the F-actin binding site in calcium-free gelsolin. Biochemical assays have indicated differences in the interaction of the C-terminal halves of adseverin and gelsolin with actin. Gelsolin contacts actin through a major site on G4 and a minor site on G6, whereas adseverin uses a site on A5. Here, we present the X-ray structure of the activated C-terminal half of adseverin (A4-A6). This structure is highly similar to that of the activated form of the C-terminal half of gelsolin (G4-G6), both in arrangement of domains and in the 3 bound calcium ions. Comparative analysis of the actin-binding surfaces observed in the G4-G6/actin structure suggests that adseverin in this conformation will also be able to interact with actin through A4 and A6, whereas the A5 surface is obscured. A single residue mutation in A4-A6 located at the predicted A4/actin interface completely abrogates actin sequestration. A model of calcium-free adseverin, constructed from the structure of gelsolin, predicts that in the absence of a gelsolin-like C-terminal extension the interaction between A2 and A6 provides the steric inhibition to prevent interaction with F-actin. We propose that calcium binding to the N terminus of adseverin dominates the activation process to expose the F-actin binding site on A2.},
	keywords = {74-KDA PROTEIN, ACTIVATION, calcium activated, EXOCYTOSIS, gelsolin, HALF, LOCALIZATION, SCINDERIN, SITE, TIRF},
	isbn = {0027-8424},
	url = {<Go to ISI>://000269078700019},
	author = {Chumnarnsilpa, S. and Lee, W. L. and Nag, S. and Kannan, B. and Larsson, M. and Burtnick, L. D. and Robinson, R. C.}
}
