{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T20:29:56Z","timestamp":1781036996727,"version":"3.54.1"},"reference-count":59,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,5,28]]},"abstract":"<jats:p>Actin bundles have profound effects on cellular shape, division, adhesion, motility, and signaling. Fimbrin belongs to a large family of actin-bundling proteins and is involved in the formation of tightly ordered cross-linked bundles in the brush border microvilli and in the stereocilia of inner ear hair cells. Polymorphism in these three-dimensional (3D) bundles has prevented the detailed structural characterization required for in-depth understanding of their morphogenesis and function. Here, we describe the structural characterization of two-dimensional arrays of actin cross-linked with human T-fimbrin. Structural information obtained by electron microscopy, x-ray crystallography, and homology modeling allowed us to build the first molecular model for the complete actin\u2013fimbrin cross-link. The restriction of the arrays to two dimensions allowed us to deduce the spatial relationship between the components, the mode of fimbrin cross-linking, and the flexibility within the cross-link. The atomic model of the fimbrin cross-link, the cross-linking rules deduced from the arrays, and the hexagonal packing of actin bundles in situ were all combined to generate an atomic model for 3D actin\u2013fimbrin bundles. Furthermore, the assembly of the actin\u2013fimbrin arrays suggests coupling between actin polymerization, fimbrin binding, and crossbridge formation, presumably achieved by a feedback between conformational changes and changes in affinity.<\/jats:p>","DOI":"10.1083\/jcb.153.5.947","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:46:23Z","timestamp":1027701983000},"page":"947-956","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":145,"title":["An Atomic Model of Actin Filaments Cross-Linked by Fimbrin and Its Implications for Bundle Assembly and Function"],"prefix":"10.1083","volume":"153","author":[{"given":"Niels","family":"Volkmann","sequence":"first","affiliation":[{"name":"aThe Burnham Institute, La Jolla, California 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"DeRosier","sequence":"additional","affiliation":[{"name":"bThe Rosenstiel Basic Medical Sciences Research Center and The W.M. Keck Institute for Cellular Visualization, Brandeis University, Waltham, Massachusetts 02254"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Matsudaira","sequence":"additional","affiliation":[{"name":"cWhitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorit","family":"Hanein","sequence":"additional","affiliation":[{"name":"aThe Burnham Institute, La Jolla, California 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2001,5,21]]},"reference":[{"key":"2023072904281953100_Ayscough1998","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/S0955-0674(98)80092-6","article-title":"In vivo functions of actin-binding proteins","volume":"10","author":"Ayscough","year":"1998","journal-title":"Curr. Opin. Cell Biol"},{"key":"2023072904281953100_Banuelosetal1998","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1016\/S0969-2126(98)00141-5","article-title":"Structural comparisons of calponin homology domainsimplications for actin binding","volume":"6","author":"Banuelos","year":"1998","journal-title":"Structure"},{"key":"2023072904281953100_Bartles2000","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/S0955-0674(99)00059-9","article-title":"Parallel actin bundles and their multiple actin-bundling proteins","volume":"12","author":"Bartles","year":"2000","journal-title":"Curr. Opin. Cell Biol"},{"key":"2023072904281953100_Bresnicketal1991","doi-asserted-by":"crossref","first-page":"12989","DOI":"10.1016\/S0021-9258(18)98793-4","article-title":"Evidence that a 27-residue sequence is the actin-binding site of ABP-120","volume":"266","author":"Bresnick","year":"1991","journal-title":"J. Biol. Chem."},{"key":"2023072904281953100_Broweretal1995","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1093\/genetics\/140.1.91","article-title":"Genetic analysis of the fimbrin-actin binding interaction in Saccharomyces cerevisiae","volume":"140","author":"Brower","year":"1995","journal-title":"Genetics."},{"key":"2023072904281953100_Carugoetal1997","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/nsb0397-175","article-title":"Crystal structure of a calponin homology domain","volume":"4","author":"Carugo","year":"1997","journal-title":"Nat. Struct. Biol"},{"key":"2023072904281953100_CastresanaandSaraste1995","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/0014-5793(95)01098-Y","article-title":"Does Vav bind to F-actin through a CH domain?","volume":"374","author":"Castresana","year":"1995","journal-title":"FEBS Lett"},{"key":"2023072904281953100_Chengetal1999","doi-asserted-by":"crossref","first-page":"35873","DOI":"10.1074\/jbc.274.50.35873","article-title":"Interaction in vivo and in vitro between the yeast fimbrin, SAC6P, and a polymerization-defective yeast actin (V266G and L267G)","volume":"274","author":"Cheng","year":"1999","journal-title":"J. Biol. Chem"},{"key":"2023072904281953100_Cohenetal1982","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1083\/jcb.95.3.987","article-title":"Schistosome surface spines are \u201ccrystals\u201d of actin","volume":"95","author":"Cohen","year":"1982","journal-title":"J. Cell Biol"},{"key":"2023072904281953100_ColuccioandBretscher1989","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1083\/jcb.108.2.495","article-title":"Reassociation of microvillar core proteinsmaking a microvillar core in vitro","volume":"108","author":"Coluccio","year":"1989","journal-title":"J. Cell Biol"},{"key":"2023072904281953100_Corradoetal1994","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/0014-5793(94)00397-1","article-title":"Deletion analysis of the dystrophin-actin binding domain","volume":"344","author":"Corrado","year":"1994","journal-title":"FEBS Lett"},{"key":"2023072904281953100_Crowtheretal1996","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1006\/jsbi.1996.0003","article-title":"MRC image processing programs","volume":"116","author":"Crowther","year":"1996","journal-title":"J. Struct. Biol."},{"key":"2023072904281953100_deArrudaetal1990","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1083\/jcb.111.3.1069","article-title":"Fimbrin is a homologue of the cytoplasmic phosphoprotein plastin and has domains homologous with calmodulin and actin gelation proteins","volume":"111","author":"de Arruda","year":"1990","journal-title":"J. Cell Biol"},{"key":"2023072904281953100_DeRosierandCensullo1981","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/0022-2836(81)90367-3","article-title":"Structure of F-actin needles from extracts of sea urchin oocytes","volume":"146","author":"DeRosier","year":"1981","journal-title":"J. Mol. Biol"},{"key":"2023072904281953100_DeRosierandTilney1982","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1101\/SQB.1982.046.01.049","article-title":"How actin filaments pack into bundles","volume":"46","author":"DeRosier","year":"1982","journal-title":"Cold Spring Harb. Symp. Quant. Biol"},{"key":"2023072904281953100_DeRosierandTilney2000","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1083\/jcb.148.1.1","article-title":"F-actin bundles are derivatives of microvilliwhat does this tell us about how bundles might form?","volume":"148","author":"DeRosier","year":"2000","journal-title":"J. Cell Biol"},{"key":"2023072904281953100_DeRosieretal1977","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/0022-2836(77)90230-3","article-title":"Structure of actin-containing filaments from two types of non-muscle cells","volume":"113","author":"DeRosier","year":"1977","journal-title":"J. Mol. Biol"},{"key":"2023072904281953100_EgelmanandDeRosier1992","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1016\/S0006-3495(92)81716-2","article-title":"Image analysis shows that variations in actins crossover spacings are random, not compensatory","volume":"63","author":"Egelman","year":"1992","journal-title":"Biophys. J"},{"key":"2023072904281953100_Fabbrizioetal1993","doi-asserted-by":"crossref","first-page":"10457","DOI":"10.1021\/bi00090a023","article-title":"Actin-dystrophin interface","volume":"32","author":"Fabbrizio","year":"1993","journal-title":"Biochemistry"},{"key":"2023072904281953100_Ferraryetal1999","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1083\/jcb.146.4.819","article-title":"In vivo, villin is required for Ca2+-dependent F-actin disruption in intestinal brush borders","volume":"146","author":"Ferrary","year":"1999","journal-title":"J. Cell Biol"},{"key":"2023072904281953100_Goldsmithetal1997","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1038\/nsb0997-708","article-title":"The structure of an actin-crosslinking domain from human fimbrin","volume":"4","author":"Goldsmith","year":"1997","journal-title":"Nat. Struct. Biol"},{"key":"2023072904281953100_Haneinetal1997","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1083\/jcb.139.2.387","article-title":"Evidence for a conformational change in actin induced by fimbrin (N375) binding","volume":"139","author":"Hanein","year":"1997","journal-title":"J. Cell Biol"},{"key":"2023072904281953100_Haneinetal1998","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/1828","article-title":"An atomic model of fimbrin binding to F-actin and its implications for filament crosslinking and regulation","volume":"5","author":"Hanein","year":"1998","journal-title":"Nat. Struct. Biol"},{"key":"2023072904281953100_Holtzmanetal1994","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1083\/jcb.126.2.423","article-title":"Mapping actin surfaces required for functional interactions in vivo","volume":"126","author":"Holtzman","year":"1994","journal-title":"J. Cell Biol."},{"key":"2023072904281953100_Hontsetal1994","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1083\/jcb.126.2.413","article-title":"Actin mutations that show suppression with fimbrin mutations identify a likely fimbrin-binding site on actin","volume":"126","author":"Honts","year":"1994","journal-title":"J. Cell Biol."},{"key":"2023072904281953100_Keepetal1999","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1016\/S0969-2126(00)88344-6","article-title":"Crystal structure of the actin-binding region of utrophin reveals a head-to-tail dimer","volume":"7","author":"Keep","year":"1999","journal-title":"Structure Fold. Des"},{"key":"2023072904281953100_Kovaretal2000","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1046\/j.1365-313x.2000.00907.x","article-title":"AtFim1 is an actin filament-crosslinking protein from Arabidopsis thaliana","volume":"24","author":"Kovar","year":"2000","journal-title":"Plant J."},{"key":"2023072904281953100_Kubaleketal1991","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/0304-3991(91)90082-H","article-title":"Improved transfer of two-dimensional crystals from the air\/water interface to specimen support grids for high-resolution analysis by electron microscopy","volume":"35","author":"Kubalek","year":"1991","journal-title":"Ultramicroscopy"},{"key":"2023072904281953100_Lebartetal1990","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/S0006-291X(05)81030-7","article-title":"Localization of a new \u03b1-actinin binding site in the COOH-terminal part of actin sequence","volume":"173","author":"Lebart","year":"1990","journal-title":"Biochem. Biophys. Res. Commun"},{"key":"2023072904281953100_Levineetal1992","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/0014-5793(92)80019-D","article-title":"Binding sites involved in the interaction of actin with the N-terminal region of dystrophin","volume":"298","author":"Levine","year":"1992","journal-title":"FEBS Lett."},{"key":"2023072904281953100_Linetal1994","first-page":"2457","article-title":"Identification of I-plastin, a human fimbrin isoform expressed in intestine and kidney","volume":"14","author":"Lin","year":"1994","journal-title":"Mol. Cell. Biol"},{"key":"2023072904281953100_Matsudaira1991","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/0968-0004(91)90039-X","article-title":"Modular organization of actin crosslinking proteins","volume":"16","author":"Matsudaira","year":"1991","journal-title":"Trends Biochem. Sci"},{"key":"2023072904281953100_Matsudaira1994","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1083\/jcb.126.2.285","article-title":"The fimbrin and \u03b1-actinin footprint on actin","volume":"126","author":"Matsudaira","year":"1994","journal-title":"J. Cell Biol."},{"key":"2023072904281953100_Matsudairaetal1983","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/301209a0","article-title":"Role of fimbrin and villin in determining the interfilament distances of actin bundles","volume":"301","author":"Matsudaira","year":"1983","journal-title":"Nature"},{"key":"2023072904281953100_McGoughetal1994","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1083\/jcb.126.2.433","article-title":"Determination of the \u03b1-actinin\u2013binding site on actin filaments by cryoelectron microscopy and image analysis","volume":"126","author":"McGough","year":"1994","journal-title":"J. Cell Biol."},{"key":"2023072904281953100_MimuraandAsano1987","doi-asserted-by":"crossref","first-page":"4717","DOI":"10.1016\/S0021-9258(18)61254-2","article-title":"Further characterization of a conserved actin-binding 27-kDa fragment of actinogelin and \u03b1-actinins and mapping of their binding sites on the actin molecule by chemical cross-linking","volume":"262","author":"Mimura","year":"1987","journal-title":"J. Biol. Chem"},{"key":"2023072904281953100_Mooresetal2000","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1006\/jmbi.2000.3583","article-title":"Structure of the utrophin actin-binding domain bound to F-actin reveals binding by an induced fit mechanism","volume":"297","author":"Moores","year":"2000","journal-title":"J. Mol. Biol"},{"key":"2023072904281953100_Nambaetal1992","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1093\/oxfordjournals.jbchem.a123929","article-title":"Human T cell L-plastin bundles actin filaments in a calcium-dependent manner","volume":"112","author":"Namba","year":"1992","journal-title":"J. Biochem."},{"key":"2023072904281953100_Norwoodetal2000","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/S0969-2126(00)00132-5","article-title":"The structure of the N-terminal actin-binding domain of human dystrophin and how mutations in this domain may cause Duchenne or Becker muscular dystrophy","volume":"8","author":"Norwood","year":"2000","journal-title":"Structure Fold. Des"},{"key":"2023072904281953100_OrlovaandEgelman2000","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1016\/S0006-3495(00)76765-8","article-title":"F-actin retains a memory of angular order","volume":"78","author":"Orlova","year":"2000","journal-title":"Biophys. J"},{"key":"2023072904281953100_Owenetal1996","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1006\/jsbi.1996.0027","article-title":"Image analysis of helical objectsthe Brandeis helical package","volume":"116","author":"Owen","year":"1996","journal-title":"J. Struct. Biol"},{"key":"2023072904281953100_Pearson1990","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/0076-6879(90)83007-V","article-title":"Rapid and sensitive sequence comparison with FASTP and FASTA","volume":"183","author":"Pearson","year":"1990","journal-title":"Methods Enzymol"},{"key":"2023072904281953100_Pinsonetal1998","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1002\/(SICI)1097-0177(199801)211:1<109::AID-AJA10>3.0.CO;2-7","article-title":"Targeted disruption of the mouse villin gene does not impair the morphogenesis of microvilli","volume":"211","author":"Pinson","year":"1998","journal-title":"Dev. Dyn"},{"key":"2023072904281953100_Puiusetal1998","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0955-0674(98)80083-5","article-title":"The modular structure of actin-regulatory proteins","volume":"10","author":"Puius","year":"1998","journal-title":"Curr. Opin. Cell Biol"},{"key":"2023072904281953100_Rostetal1998","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S0304-3991(98)00017-5","article-title":"Reconstruction of symmetry deviationsa procedure to analyze partially decorated F-actin and other incomplete structures","volume":"72","author":"Rost","year":"1998","journal-title":"Ultramicroscopy"},{"key":"2023072904281953100_Rozyckietal1991","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/0076-6879(91)96012-G","article-title":"Affinity chromatography-based purification of profilin:actin","volume":"196","author":"Rozycki","year":"1991","journal-title":"Methods Enzymol"},{"key":"2023072904281953100_SaliandBlundell1993","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1006\/jmbi.1993.1626","article-title":"Comparative protein modelling by satisfaction of spatial restraints","volume":"234","author":"Sali","year":"1993","journal-title":"J. Mol. Biol"},{"key":"2023072904281953100_Smith1999","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1006\/jsbi.1998.4073","article-title":"Ximdisp\u2014a visualization tool to aid structure determination from electron microscope images","volume":"125","author":"Smith","year":"1999","journal-title":"J. Struct. Biol"},{"key":"2023072904281953100_SpudichandAmos1979","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/0022-2836(79)90285-7","article-title":"Structure of actin filament bundles from microvilli of sea urchin eggs","volume":"129","author":"Spudich","year":"1979","journal-title":"J. Mol. Biol"},{"key":"2023072904281953100_SukowandDeRosier1998","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1006\/jmbi.1998.2211","article-title":"How to analyze electron micrographs of rafts of actin filaments crosslinked by actin-binding proteins","volume":"284","author":"Sukow","year":"1998","journal-title":"J. Mol. Biol"},{"key":"2023072904281953100_TaylorandTaylor1994","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1016\/S0006-3495(94)80680-0","article-title":"Formation of two-dimensional complexes of F-actin and crosslinking proteins on lipid monolayersdemonstration of unipolar \u03b1-actinin-F-actin crosslinking","volume":"67","author":"Taylor","year":"1994","journal-title":"Biophys. J"},{"key":"2023072904281953100_Tayloretal2000","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1083\/jcb.149.3.635","article-title":"Isoforms of \u03b1-actinin from cardiac, smooth, and skeletal muscle form polar arrays of actin filaments","volume":"149","author":"Taylor","year":"2000","journal-title":"J. Cell Biol"},{"key":"2023072904281953100_Tilneyetal1980","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1083\/jcb.86.1.244","article-title":"The organization of actin filaments in the stereocilia of cochlear hair cells","volume":"86","author":"Tilney","year":"1980","journal-title":"J. Cell Biol"},{"key":"2023072904281953100_Tilneyetal1983","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1083\/jcb.96.3.822","article-title":"Actin filaments, stereocilia, and hair cells of the bird cochlea. II. Packing of actin filaments in the stereocilia and in the cuticular plate and what happens to the organization when the stereocilia are bent","volume":"96","author":"Tilney","year":"1983","journal-title":"J. Cell Biol"},{"key":"2023072904281953100_Tilneyetal1989","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1083\/jcb.109.4.1711","article-title":"Preliminary biochemical characterization of the stereocilia and cuticular plate of hair cells of the chick cochlea","volume":"109","author":"Tilney","year":"1989","journal-title":"J. Cell Biol"},{"key":"2023072904281953100_Tilneyetal1992","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1146\/annurev.cb.08.110192.001353","article-title":"Actin filaments, stereocilia, and hair cellshow cells count and measure","volume":"8","author":"Tilney","year":"1992","journal-title":"Annu. Rev. Cell Biol"},{"key":"2023072904281953100_Tilneyetal2000","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1083\/jcb.148.1.87","article-title":"Regulation of actin filament cross-linking and bundle shape in Drosophila bristles","volume":"148","author":"Tilney","year":"2000","journal-title":"J. Cell Biol"},{"key":"2023072904281953100_Wardetal1990","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1002\/jemt.1060140408","article-title":"Method for forming two-dimensional paracrystals of biological filaments on lipid monolayers","volume":"14","author":"Ward","year":"1990","journal-title":"J. Electron Microsc. Tech"},{"key":"2023072904281953100_Yapetal1999","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1002\/(SICI)1097-0134(19991115)37:3<499::AID-PROT17>3.0.CO;2-Y","article-title":"Diversity of conformational states and changes within the EF-hand protein superfamily","volume":"37","author":"Yap","year":"1999","journal-title":"Proteins"}],"container-title":["The Journal of Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jcb\/article-pdf\/153\/5\/947\/1864406\/0011050.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jcb\/article-pdf\/153\/5\/947\/1864406\/0011050.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,29]],"date-time":"2023-07-29T04:29:26Z","timestamp":1690604966000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jcb\/article\/153\/5\/947\/45997\/An-Atomic-Model-of-Actin-Filaments-Cross-Linked-by"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,5,21]]},"references-count":59,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2001,5,28]]}},"URL":"https:\/\/doi.org\/10.1083\/jcb.153.5.947","relation":{},"ISSN":["0021-9525","1540-8140"],"issn-type":[{"value":"0021-9525","type":"print"},{"value":"1540-8140","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,5,21]]}}}