@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 {891,
	title = {Structural basis of actin sequestration by thymosin-beta 4: implications for WH2 proteins},
	journal = {Embo Journal},
	volume = {23},
	number = {18},
	year = {2004},
	note = {ISI Document Delivery No.: 861IFTimes Cited: 48Cited Reference Count: 51},
	month = {Sep},
	pages = {3599-3608},
	type = {Article},
	abstract = {The WH2 (Wiscott - Aldridge syndrome protein homology domain 2) repeat is an actin interacting motif found in monomer sequestering and filament assembly proteins. We have stabilized the prototypical WH2 family member, thymosin-beta4 (Tbeta4), with respect to actin, by creating a hybrid between gelsolin domain 1 and the C-terminal half of Tbeta4 (G1-Tbeta4). This hybrid protein sequesters actin monomers, severs actin filaments and acts as a leaky barbed end cap. Here, we present the structure of the G1-Tbeta4: actin complex at 2Angstrom resolution. The structure reveals that Tbeta4 sequesters by capping both ends of the actin monomer, and that exchange of actin between Tb4 and profilin is mediated by a minor overlap in binding sites. The structure implies that multiple WH2 motif-containing proteins will associate longitudinally with actin filaments. Finally, we discuss the role of the WH2 motif in arp2/3 activation.},
	keywords = {actin, ARP2/3 COMPLEX, BETA-THYMOSINS, BINDING-PROTEINS, CRYSTAL-STRUCTURE, DNASE-I, F-ACTIN, MONOMERIC, NEGATIVE COOPERATIVITY, NMR-SPECTROSCOPY, NUCLEAR-MAGNETIC-RESONANCE, protein crystallography, SCAR, VCA, WASp, WH2},
	isbn = {0261-4189},
	url = {<Go to ISI>://000224409100003},
	author = {Irobi, E. and Aguda, A. H. and Larsson, M. and Guerin, C. and Yin, H. L. and Burtnick, L. D. and Blanchoin, L. 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 {697,
	title = {Activation in isolation: exposure of the actin-binding site in the C-terminal half of gelsolin does not require actin},
	journal = {Febs Letters},
	volume = {552},
	number = {2-3},
	year = {2003},
	note = {ISI Document Delivery No.: 726DKTimes Cited: 15Cited Reference Count: 23},
	month = {Sep},
	pages = {82-85},
	type = {Article},
	abstract = {Gelsolin requires activation to carry out its severing and capping activities on F-actin. Here, we present the structure of the isolated C-terminal half of gelsolin (G4-G6) at 2.0 resolution in the presence of Ca2+ ions. This structure completes a triptych of the states of activation of G4-G6 that illuminates its role in the function of gelsolin. Activated G4-G6 displays an open conformation, with the actin-binding site on G4 fully exposed and all three type-2 Ca2+ sites occupied. Neither actin nor the type-1 Ca2+, which normally is sandwiched between actin and G4, is required to achieve this conformation. (C) 2003 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.},
	keywords = {actin, calcium-activation, COMPLEX, DOMAINS, F-ACTIN, gelsolin, PLASMA GELSOLIN, REGULATORY PROTEIN, TRANSFORMATION},
	isbn = {0014-5793},
	url = {<Go to ISI>://000185583000002},
	author = {Narayan, K. and Chumnarnsilpa, S. and Choe, H. and Irobi, E. and Urosev, D. and Lindberg, U. and Schutt, C. E. and Burtnick, L. D. and Robinson, R. C.}
}
@article {643,
	title = {From the first to the second domain of gelsolin: a common path on the surface of actin?},
	journal = {Febs Letters},
	volume = {552},
	number = {2-3},
	year = {2003},
	note = {ISI Document Delivery No.: 726DKTimes Cited: 22Cited Reference Count: 29},
	month = {Sep},
	pages = {86-90},
	type = {Article},
	abstract = {We present the 2.6. resolution crystal structure of a complex formed between G-actin and gelsolin fragment Met25-GIn160 (G1+). The structure differs from those of other gelsolin domain 1 (G1) complexes in that an additional six amino acid residues from the crucial linker region into gelsolin domain 2 (G2) are visible and are attached securely to the surface of actin. The linker segment extends away from G1 up the face of actin in a direction that infers G2 will bind along the same long-pitch helical strand as the actin bound to G1. This is consistent with a mechanism whereby G2 attaches gelsolin to the side of a filament and then directs G1 toward a position where it would disrupt actin-actin contacts. Alignment of the sequence of the structurally important residues within the G1-G2 linker with those of WH2 (WASp homology domain 2) domain protein family members (e.g. WASp (Wiscott-Aldridge syndrome protein) and thymosin beta4) suggests that the opposing activities of filament assembly and disassembly may exploit a common patch on the surface of actin. (C) 2003 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.},
	keywords = {actin, BINDING, calcium, COMPLEX, crystal structure, DIFFRACTION DATA, F-ACTIN, FILAMENT, gelsolin, IDENTIFICATION, MODEL, MOTILITY, NUCLEATION, WH2 domain},
	isbn = {0014-5793},
	url = {<Go to ISI>://000185583000003},
	author = {Irobi, E. and Burtnick, L. D. and Urosev, D. 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.}
}
@article {5048,
	title = {Cdc4p, a contractile ring protein essential for cytokinesis in Schizosaccharomyces pombe, interacts with a phosphatidylinositol 4-kinase},
	journal = {Journal of Biological Chemistry},
	volume = {276},
	number = {8},
	year = {2001},
	note = {ISI Document Delivery No.: 404RUTimes Cited: 27Cited Reference Count: 35},
	month = {Feb},
	pages = {5932-5942},
	type = {Article},
	abstract = {The proposed function of Cdc4p, an essential contractile ring protein in Schizosaccharomyces pombe, is that of a myosin essential light chain. However, five conditionally lethal cdc4 alleles exhibit complementation in diploids. Such interallelic complementation is not readily explained if the sole function of Cde4p is that of a myosin essential light chain. Complementation of cdc4 alleles could occur only if different mutant forms can assemble into an active oligomeric complex or if Cdc4p has more than one essential function. To search for other proteins that may interact with Cdc4p, we performed a two-hybrid screen and identified two such candidates: one similar to Saccharomyces cerevisiae Vps27p and the other a putative phosphatidylinositol (PI) 4-kinase. finding of Cdc4p to the latter and to myosin heavy chain (Myo2p) was confirmed by immunosorbent assays. Deletion studies demonstrated interaction between the Cdc4p C-terminal domain and the PI 4-kinase C-terminal domain. Furthermore, interaction was abolished by the Cdc4p C-terminal domain point mutation, Gly(107) to Ser. This allele also causes failure of cytokinesis. Ectopic expression of the PI 4-kinase C-terminal domain caused cytokinesis defects that were most extreme in cells carrying the G107S allele. We suggest that Cdc4p plays multiple roles in cytokinesis and that interaction with a PI I-kinase may be important for contractile ring assembly and/or function.},
	keywords = {ACTOMYOSIN RING, BINDING, CELL-DIVISION CYCLE, F-ACTIN, FISSION YEAST, GENE, IDENTIFICATION, LIGHT-CHAIN, LOCALIZATION, MYOSIN HEAVY-CHAIN},
	isbn = {0021-9258},
	url = {<Go to ISI>://000167115100071},
	author = {Desautels, M. and Den Haese, J. P. and Slupsky, C. M. and McIntosh, L. P. and Hemmingsen, S. M.}
}
@article {3920,
	title = {The crystal structure of plasma gelsolin: Implications for actin severing, capping, and nucleation},
	journal = {Cell},
	volume = {90},
	number = {4},
	year = {1997},
	note = {ISI Document Delivery No.: XT066Times Cited: 164Cited Reference Count: 50},
	month = {Aug},
	pages = {661-670},
	type = {Article},
	abstract = {The structure of gelsolin has been determined by crystallography and comprises six structurally related domains that, in a Ca2+-free environment, pack together to form a compact globular structure in which the putative actin-binding sequences are not sufficiently exposed to enable binding to occur. We propose that binding Ca2+ can release the connections that join the N- and C-terminal halves of gelsolin, enabling each half to bind actin relatively independently. Domain shifts are proposed in response to Ca2+ as bases for models of how gelsolin acts to sever, cap, or nucleate F-actin filaments. The structure also invites discussion of polyphosphoinositide binding to segment 2 and suggests how mutation at Asp-187 could initiate a series of events that lead to deposition of amyloid plaques, as observed in victims of familial amyloidosis (Finnish type).},
	keywords = {AMYLOIDOSIS, BINDING DOMAIN, calcium, DEFINITION, F-ACTIN, FILAMENT, IDENTIFICATION, PROTEIN, SEQUENCE, VILLIN},
	isbn = {0092-8674},
	url = {<Go to ISI>://A1997XT06600010},
	author = {Burtnick, L. D. and Koepf, E. K. and Grimes, J. and Jones, E. Y. and Stuart, D. I. and McLaughlin, P. J. and Robinson, R. C.}
}
@article {6992,
	title = {HYBRIDIZATION OF RABBIT CARDIAC TROPOMYOSIN WITH NONPOLYMERIZABLE TROPOMYOSIN SPECIES},
	journal = {Biochemistry International},
	volume = {23},
	number = {4},
	year = {1991},
	note = {ISI Document Delivery No.: FR332Times Cited: 0Cited Reference Count: 19},
	month = {Mar},
	pages = {801-807},
	type = {Article},
	keywords = {ALPHA-TROPOMYOSIN, AMINO-ACID-SEQUENCE, BETA-TROPOMYOSIN, BINDING, EQUINE PLATELET TROPOMYOSIN, EXCIMER FLUORESCENCE, F-ACTIN, MUSCLE},
	isbn = {0158-5231},
	url = {<Go to ISI>://A1991FR33200022},
	author = {Clark, I. D. and Burtnick, L. D.}
}
