| 词条 | Gelsolin |
| 释义 |
| Symbol = Gelsolin | Name = Gelsolin | image = PDB 1pd0 EBI.jpg | width = | caption = crystal structure of the copii coat subunit, sec24, complexed with a peptide from the snare protein sed5 (yeast syntaxin-5) | Pfam = PF00626 | Pfam_clan = CL0092 | InterPro = IPR007123 | SMART = | PROSITE = | MEROPS = | SCOP = 1vil | TCDB = | OPM family = | OPM protein = | CAZy = | CDD = }}{{Infobox_gene}}Gelsolin is an actin-binding protein that is a key regulator of actin filament assembly and disassembly. Gelsolin is one of the most potent members of the actin-severing gelsolin/villin superfamily, as it severs with nearly 100% efficiency.[1][2] Gelsolin is located intracellularly (in cytosol and mitochondria) and extracellularly (in blood plasma).[3] StructureGelsolin is an 82-kD protein with six homologous subdomains, referred to as S1-S6. Each subdomain is composed of a five-stranded β-sheet, flanked by two α-helices, one positioned perpendicular with respect to the strands and one positioned parallel. The β-sheets of the three N-terminal subdomains (S1-S3) join to form an extended β-sheet, as do the β-sheets of the C-terminal subdomains (S4-S6).[4] RegulationAmong the lipid-binding actin regulatory proteins, gelsolin (like cofilin) preferentially binds polyphosphoinositide (PPI).[5] The binding sequences in gelsolin closely resemble the motifs in the other PPI-binding proteins.[5] Gelsolin's activity is stimulated by calcium ions (Ca2+).[2] Although the protein retains its overall structural integrity in both activated and deactivated states, the S6 helical tail moves like a latch depending on the concentration of calcium ions.[6] The C-terminal end detects the calcium concentration within the cell. When there is no Ca2+ present, the tail of S6 shields the actin-binding sites on one of S2's helices.[4] When a calcium ion attaches to the S6 tail, however, it straightens, exposing the S2 actin-binding sites.[6] The N-terminal is directly involved in the severing of actin. S2 and S3 bind to the actin before the binding of S1 severs actin-actin bonds and caps the barbed end.[5] Gelsolin can be inhibited by a local rise in the concentration of phosphatidylinositol (4,5)-bisphosphate (PIP2), a PPI. This is a two step process. Firstly, (PIP2) binds to S2 and S3, inhibiting gelsolin from actin side binding. Then, (PIP2) binds to gelsolin’s S1, preventing gelsolin from severing actin, although (PIP2) does not bind directly to gelsolin's actin-binding site.[5] Gelsolin's severing of actin, in contrast to the severing of microtubules by katanin, does not require any extra energy input. Cellular functionAs an important actin regulator, gelsolin plays a role in podosome formation (along with Arp3, cortactin, and Rho GTPases).[7] Gelsolin also inhibits apoptosis by stabilizing the mitochondria.[3] Prior to cell death, mitochondria normally lose membrane potential and become more permeable. Gelsolin can impede the release of cytochrome C, obstructing the signal amplification that would have led to apoptosis.[8] Actin can be cross-linked into a gel by actin cross-linking proteins. Gelsolin can turn this gel into a sol, hence the name gelsolin. Animal studiesResearch in mice suggests that gelsolin, like other actin-severing proteins, is not expressed to a significant degree until after the early embryonic stage—approximately 2 weeks in murine embryos.[9] In adult specimens, however, gelsolin is particularly important in motile cells, such as blood platelets. Mice with null gelsolin-coding genes undergo normal embryonic development, but the deformation of their blood platelets reduced their motility, resulting in a slower response to wound healing.[9] An insufficiency of gelsolin in mice has also been shown to cause increased permeability of the vascular pulmonary barrier, suggesting that gelsolin is important in the response to lung injury.[10] Related proteinsSequence comparisons indicate an evolutionary relationship between gelsolin, villin, fragmin and severin.[11] Six large repeating segments occur in gelsolin and villin, and 3 similar segments in severin and fragmin. While the multiple repeats have yet to be related to any known function of the actin-severing proteins, the superfamily appears to have evolved from an ancestral sequence of 120 to 130 amino acid residues.[1][11]InteractionsGelsolin is a cytoplasmic, calcium-regulated, actin-modulating protein that binds to the barbed ends of actin filaments, preventing monomer exchange (end-blocking or capping).[12] It can promote nucleation (the assembly of monomers into filaments), as well as sever existing filaments. In addition, this protein binds with high affinity to fibronectin. Plasma gelsolin and cytoplasmic gelsolin are derived from a single gene by alternate initiation sites and differential splicing. Gelsolin has been shown to interact with:
See also
References1. ^1 {{cite journal | authors = Ghoshdastider U, Popp D, Burtnick LD, Robinson RC | title = The expanding superfamily of gelsolin homology domain proteins | journal = Cytoskeleton | volume = 70 | issue = 11 | pages = 775–95 | year = 2013 | pmid = 24155256 | doi = 10.1002/cm.21149 }} 2. ^1 {{cite journal | vauthors = Sun HQ, Yamamoto M, Mejillano M, Yin HL | title = Gelsolin, a multifunctional actin regulatory protein | journal = J. Biol. Chem. | volume = 274 | issue = 47 | pages = 33179–82 | date = November 1999 | pmid = 10559185 | doi = 10.1074/jbc.274.47.33179 }} 3. ^1 {{cite journal | vauthors = Koya RC, Fujita H, Shimizu S, Ohtsu M, Takimoto M, Tsujimoto Y, Kuzumaki N | title = Gelsolin inhibits apoptosis by blocking mitochondrial membrane potential loss and cytochrome c release | journal = J. Biol. Chem. | volume = 275 | issue = 20 | pages = 15343–9 | date = May 2000 | pmid = 10809769 | doi = 10.1074/jbc.275.20.15343 }} 4. ^1 {{cite journal | vauthors = Kiselar JG, Janmey PA, Almo SC, Chance MR | title = Visualizing the Ca2+-dependent activation of gelsolin by using synchrotron footprinting | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 100 | issue = 7 | pages = 3942–7 | date = April 2003 | pmid = 12655044 | pmc = 153027 | doi = 10.1073/pnas.0736004100 }} 5. ^1 2 3 {{cite journal | vauthors = Yu FX, Sun HQ, Janmey PA, Yin HL | title = Identification of a polyphosphoinositide-binding sequence in an actin monomer-binding domain of gelsolin | journal = J. Biol. Chem. | volume = 267 | issue = 21 | pages = 14616–21 | date = July 1992 | pmid = 1321812 | doi = }} 6. ^1 {{cite journal | vauthors = Burtnick LD, Urosev D, Irobi E, Narayan K, Robinson RC | title = Structure of the N-terminal half of gelsolin bound to actin: roles in severing, apoptosis and FAF | journal = EMBO J. | volume = 23 | issue = 14 | pages = 2713–22 | date = July 2004 | pmid = 15215896 | pmc = 514944 | doi = 10.1038/sj.emboj.7600280 }} 7. ^{{cite journal | vauthors = Varon C, Tatin F, Moreau V, Van Obberghen-Schilling E, Fernandez-Sauze S, Reuzeau E, Kramer I, Génot E | title = Transforming growth factor beta induces rosettes of podosomes in primary aortic endothelial cells | journal = Mol. Cell. Biol. | volume = 26 | issue = 9 | pages = 3582–94 | date = May 2006 | pmid = 16611998 | pmc = 1447430 | doi = 10.1128/MCB.26.9.3582-3594.2006 }} 8. ^1 {{cite journal | vauthors = Kusano H, Shimizu S, Koya RC, Fujita H, Kamada S, Kuzumaki N, Tsujimoto Y | title = Human gelsolin prevents apoptosis by inhibiting apoptotic mitochondrial changes via closing VDAC | journal = Oncogene | volume = 19 | issue = 42 | pages = 4807–14 | date = October 2000 | pmid = 11039896 | doi = 10.1038/sj.onc.1203868 }} 9. ^1 {{cite journal | vauthors = Witke W, Sharpe AH, Hartwig JH, Azuma T, Stossel TP, Kwiatkowski DJ | title = Hemostatic, inflammatory, and fibroblast responses are blunted in mice lacking gelsolin | journal = Cell | volume = 81 | issue = 1 | pages = 41–51 | date = April 1995 | pmid = 7720072 | doi = 10.1016/0092-8674(95)90369-0 }} 10. ^{{cite journal | vauthors = Becker PM, Kazi AA, Wadgaonkar R, Pearse DB, Kwiatkowski D, Garcia JG | title = Pulmonary vascular permeability and ischemic injury in gelsolin-deficient mice | journal = Am. J. Respir. Cell Mol. Biol. | volume = 28 | issue = 4 | pages = 478–84 | date = April 2003 | pmid = 12654637 | doi = 10.1165/rcmb.2002-0024OC }} 11. ^1 {{cite journal | vauthors = Way M, Weeds A | title = Nucleotide sequence of pig plasma gelsolin. Comparison of protein sequence with human gelsolin and other actin-severing proteins shows strong homologies and evidence for large internal repeats | journal = J. Mol. Biol. | volume = 203 | issue = 4 | pages = 1127–33 | date = October 1988 | pmid = 2850369 | doi = 10.1016/0022-2836(88)90132-5 }} 12. ^{{cite journal | vauthors = Weeds AG, Gooch J, Pope B, Harris HE | title = Preparation and characterization of pig plasma and platelet gelsolins | journal = Eur. J. Biochem. | volume = 161 | issue = 1 | pages = 69–76 | date = November 1986 | pmid = 3023087 | doi = 10.1111/j.1432-1033.1986.tb10125.x }} 13. ^{{cite journal | vauthors = Chauhan VP, Ray I, Chauhan A, Wisniewski HM | title = Binding of gelsolin, a secretory protein, to amyloid beta-protein | journal = Biochem. Biophys. Res. Commun. | volume = 258 | issue = 2 | pages = 241–6 | date = May 1999 | pmid = 10329371 | doi = 10.1006/bbrc.1999.0623 }} 14. ^{{cite journal | vauthors = Nishimura K, Ting HJ, Harada Y, Tokizane T, Nonomura N, Kang HY, Chang HC, Yeh S, Miyamoto H, Shin M, Aozasa K, Okuyama A, Chang C | title = Modulation of androgen receptor transactivation by gelsolin: a newly identified androgen receptor coregulator | journal = Cancer Res. | volume = 63 | issue = 16 | pages = 4888–94 | date = August 2003 | pmid = 12941811 | doi = }} 15. ^{{cite journal | vauthors = Wang Q, Xie Y, Du QS, Wu XJ, Feng X, Mei L, McDonald JM, Xiong WC | title = Regulation of the formation of osteoclastic actin rings by proline-rich tyrosine kinase 2 interacting with gelsolin | journal = J. Cell Biol. | volume = 160 | issue = 4 | pages = 565–75 | date = February 2003 | pmid = 12578912 | pmc = 2173747 | doi = 10.1083/jcb.200207036 }} External links
1 : Proteins |
| 随便看 |
|
开放百科全书收录14589846条英语、德语、日语等多语种百科知识，基本涵盖了大多数领域的百科知识，是一部内容自由、开放的电子版国际百科全书。