| http://purl.uniprot.org/citations/19666512 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/19666512 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/19666512 | http://www.w3.org/2000/01/rdf-schema#comment | "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 Ca(2+) 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 Ca(2+) 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."xsd:string |
| http://purl.uniprot.org/citations/19666512 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.0812374106"xsd:string |
| http://purl.uniprot.org/citations/19666512 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.0812374106"xsd:string |
| http://purl.uniprot.org/citations/19666512 | http://purl.uniprot.org/core/author | "Robinson R.C."xsd:string |
| http://purl.uniprot.org/citations/19666512 | http://purl.uniprot.org/core/author | "Robinson R.C."xsd:string |
| http://purl.uniprot.org/citations/19666512 | http://purl.uniprot.org/core/author | "Nag S."xsd:string |
| http://purl.uniprot.org/citations/19666512 | http://purl.uniprot.org/core/author | "Nag S."xsd:string |
| http://purl.uniprot.org/citations/19666512 | http://purl.uniprot.org/core/author | "Wang H."xsd:string |
| http://purl.uniprot.org/citations/19666512 | http://purl.uniprot.org/core/author | "Wang H."xsd:string |
| http://purl.uniprot.org/citations/19666512 | http://purl.uniprot.org/core/author | "Ma Q."xsd:string |
| http://purl.uniprot.org/citations/19666512 | http://purl.uniprot.org/core/author | "Ma Q."xsd:string |
| http://purl.uniprot.org/citations/19666512 | http://purl.uniprot.org/core/author | "Hernandez-Valladares M."xsd:string |
| http://purl.uniprot.org/citations/19666512 | http://purl.uniprot.org/core/author | "Hernandez-Valladares M."xsd:string |
| http://purl.uniprot.org/citations/19666512 | http://purl.uniprot.org/core/author | "Larsson M."xsd:string |
| http://purl.uniprot.org/citations/19666512 | http://purl.uniprot.org/core/author | "Larsson M."xsd:string |
| http://purl.uniprot.org/citations/19666512 | http://purl.uniprot.org/core/author | "Kannan B."xsd:string |
| http://purl.uniprot.org/citations/19666512 | http://purl.uniprot.org/core/author | "Kannan B."xsd:string |
| http://purl.uniprot.org/citations/19666512 | http://purl.uniprot.org/core/author | "Lee W.L."xsd:string |
| http://purl.uniprot.org/citations/19666512 | http://purl.uniprot.org/core/author | "Lee W.L."xsd:string |
| http://purl.uniprot.org/citations/19666512 | http://purl.uniprot.org/core/author | "Burtnick L.D."xsd:string |
| http://purl.uniprot.org/citations/19666512 | http://purl.uniprot.org/core/author | "Burtnick L.D."xsd:string |
| http://purl.uniprot.org/citations/19666512 | http://purl.uniprot.org/core/author | "Chumnarnsilpa S."xsd:string |
| http://purl.uniprot.org/citations/19666512 | http://purl.uniprot.org/core/author | "Chumnarnsilpa S."xsd:string |