{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:58:46Z","timestamp":1788872326899,"version":"build-2803163510"},"reference-count":54,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T00:00:00Z","timestamp":1104537600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T00:00:00Z","timestamp":1104537600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2013,7,16]],"date-time":"2013-07-16T00:00:00Z","timestamp":1373932800000},"content-version":"vor","delay-in-days":3118,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100001868","name":"National Science Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001868","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011912","name":"Taipei Veterans General Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011912","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biophysical Journal"],"published-print":{"date-parts":[[2005,1]]},"DOI":"10.1529\/biophysj.104.046813","type":"journal-article","created":{"date-parts":[[2004,10,8]],"date-time":"2004-10-08T20:13:56Z","timestamp":1097266436000},"page":"455-466","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":50,"title":["Structural Variation in Human Apolipoprotein E3 and E4: Secondary Structure, Tertiary Structure, and Size Distribution"],"prefix":"10.1016","volume":"88","author":[{"given":"Chi-Yuan","family":"Chou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ling","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Chyi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheh-Yi","family":"Sheu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ta-Hsien","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huey-Jen","family":"Tsay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gu-Gang","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Shi","family":"Shiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1529\/biophysj.104.046813_bib1","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1093\/protein\/6.4.383","article-title":"Evaluation of secondary structure of proteins from UV circular dichroism using an unsupervised learning neural network","volume":"6","author":"Andrade","year":"1993","journal-title":"Protein Eng."},{"key":"10.1529\/biophysj.104.046813_bib2","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1042\/bj0550644","article-title":"Sedimentation coefficients of small molecules: methods of measurement based on the refractive-index gradient curve. The sedimentation coefficient of polyglucose A","volume":"55","author":"Baldwin","year":"1953","journal-title":"Biochem. J."},{"key":"10.1529\/biophysj.104.046813_bib3","first-page":"31","article-title":"Site-directed mutagenesis using double-stranded plasmid DNA templates","volume":"57","author":"Braman","year":"1996","journal-title":"Methods Mol. Biol."},{"key":"10.1529\/biophysj.104.046813_bib4","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1194\/jlr.R300010-JLR200","article-title":"Membrane dynamics, cholesterol homeostasis, and Alzheimer\u2019s disease","volume":"44","author":"Chauhan","year":"2003","journal-title":"J. Lipid Res."},{"key":"10.1529\/biophysj.104.046813_bib5","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.jmb.2003.09.059","article-title":"Inter-molecular coiled-coil formation in human apolipoprotein E C-terminal domain","volume":"334","author":"Choy","year":"2004","journal-title":"J. Mol. Biol."},{"key":"10.1529\/biophysj.104.046813_bib6","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/0003-9861(69)90157-X","article-title":"Computer simulation of sedimentation in the ultracentrifuge. IV. Velocity sedimentation of self-associating solutes","volume":"129","author":"Cox","year":"1969","journal-title":"Arch. Biochem. Biophys."},{"key":"10.1529\/biophysj.104.046813_bib7","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1172\/JCI115459","article-title":"Influence of apolipoprotein E polymorphism on apolipoprotein B-100 metabolism in normolipemic subjects","volume":"88","author":"Demant","year":"1991","journal-title":"J. Clin. Invest."},{"key":"10.1529\/biophysj.104.046813_bib8","first-page":"251","article-title":"Composition and structural and functional properties of discoidal and spherical phospholipid-apoE3 complexes","volume":"62","author":"De Pauw","year":"1997","journal-title":"Biochemistry (Mosc.)."},{"key":"10.1529\/biophysj.104.046813_bib9","doi-asserted-by":"crossref","first-page":"19053","DOI":"10.1074\/jbc.271.32.19053","article-title":"Human apolipoprotein E4 domain interaction. Arginine 61 and glutamic acid 255 interact to direct the preference for very low density lipoproteins","volume":"271","author":"Dong","year":"1996","journal-title":"J. Biol. Chem."},{"key":"10.1529\/biophysj.104.046813_bib10","doi-asserted-by":"crossref","first-page":"22358","DOI":"10.1016\/S0021-9258(17)31797-0","article-title":"Human apolipoprotein E. Role of arginine 61 in mediating the lipoprotein preferences of the E3 and E4 isoforms","volume":"269","author":"Dong","year":"1994","journal-title":"J. Biol. Chem."},{"key":"10.1529\/biophysj.104.046813_bib11","doi-asserted-by":"crossref","first-page":"5055","DOI":"10.1021\/bi035958w","article-title":"A monomeric human apolipoprotein E carboxyl-terminal domain","volume":"43","author":"Fan","year":"2004","journal-title":"Biochemistry"},{"key":"10.1529\/biophysj.104.046813_bib12","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1194\/jlr.M400104-JLR200","article-title":"The recycling of apolipoprotein E and its amino-terminal 22 kDa fragment: evidence for multiple redundant pathways","volume":"45","author":"Farkas","year":"2004","journal-title":"J. Lipid Res."},{"key":"10.1529\/biophysj.104.046813_bib13","series-title":"Foundations of Ultracentrifugal Analysis","author":"Fujita","year":"1975"},{"key":"10.1529\/biophysj.104.046813_bib14","doi-asserted-by":"crossref","first-page":"9382","DOI":"10.1073\/pnas.91.20.9382","article-title":"Neuropathology and apolipoprotein E profile of aged chimpanzees: implications for Alzheimer disease","volume":"91","author":"Gearing","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1529\/biophysj.104.046813_bib15","doi-asserted-by":"crossref","first-page":"10966","DOI":"10.1073\/pnas.1434398100","article-title":"Carboxyl-terminal-truncated apolipoprotein E4 causes Alzheimer\u2019s disease-like neurodegeneration and behavioral deficits in transgenic mice","volume":"100","author":"Harris","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1529\/biophysj.104.046813_bib16","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1016\/S0140-6736(95)92405-1","article-title":"Apolipoprotein E allele epsilon 4, dementia, and cognitive decline in a population sample","volume":"346","author":"Henderson","year":"1995","journal-title":"Lancet"},{"key":"10.1529\/biophysj.104.046813_bib17","doi-asserted-by":"crossref","first-page":"8838","DOI":"10.1073\/pnas.151254698","article-title":"Apolipoprotein E fragments present in Alzheimer\u2019s disease brains induce neurofibrillary tangle-like intracellular inclusions in neurons","volume":"98","author":"Huang","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"10.1529\/biophysj.104.046813_bib18","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0021-9150(94)05464-T","article-title":"The effects of apolipoprotein E polymorphism on the distribution of lipids and lipoproteins in the Chinese population","volume":"114","author":"Kao","year":"1995","journal-title":"Atherosclerosis"},{"key":"10.1529\/biophysj.104.046813_bib19","doi-asserted-by":"crossref","first-page":"8447","DOI":"10.1016\/S0021-9258(18)81806-3","article-title":"Human apolipoprotein E. Receptor binding activity of truncated variants with carboxyl-terminal deletions","volume":"264","author":"Lalazar","year":"1989","journal-title":"J. Biol. Chem."},{"key":"10.1529\/biophysj.104.046813_bib20","first-page":"1","article-title":"Die differentialgleichung der ultrazentrifugierung","volume":"21B","author":"Lamm","year":"1929","journal-title":"Ark. Mat. Astr. Fys."},{"key":"10.1529\/biophysj.104.046813_bib21","series-title":"Analytical Ultracentrifugation in Biochemistry and Polymer Science","first-page":"90","article-title":"Computer-aided interpretation of analytical sedimentation data for proteins","author":"Laue","year":"1992"},{"key":"10.1529\/biophysj.104.046813_bib22","doi-asserted-by":"crossref","first-page":"10406","DOI":"10.1021\/bi027093c","article-title":"Domains of apoE required for binding to apoE receptor 2 and to phospholipids: Implication for the functions of apoE in the brain","volume":"42","author":"Li","year":"2003","journal-title":"Biochemistry"},{"key":"10.1529\/biophysj.104.046813_bib23","first-page":"373","article-title":"A website for the analysis of protein secondary structure from circular dichroism spectra","volume":"80","author":"Lobley","year":"2001","journal-title":"Biophys. J."},{"key":"10.1529\/biophysj.104.046813_bib24","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1093\/bioinformatics\/18.1.211","article-title":"DICHROWEB: an interactive website for the analysis of protein secondary structure from circular dichroism spectra","volume":"18","author":"Lobley","year":"2002","journal-title":"Bioinformatics"},{"key":"10.1529\/biophysj.104.046813_bib25","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1126\/science.8424167","article-title":"Alzheimer\u2019s pathology begins to yield its secrets","volume":"259","author":"Marx","year":"1993","journal-title":"Science"},{"key":"10.1529\/biophysj.104.046813_bib26","doi-asserted-by":"crossref","first-page":"50380","DOI":"10.1074\/jbc.M204898200","article-title":"Apolipoprotein E4 forms a molten globule. A potential basis for its association with disease","volume":"277","author":"Morrow","year":"2002","journal-title":"J. Biol. Chem."},{"key":"10.1529\/biophysj.104.046813_bib27","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1126\/science.8171342","article-title":"Differential effects of apolipoproteins E3 and E4 on neuronal growth in vitro","volume":"264","author":"Nathan","year":"1994","journal-title":"Science"},{"key":"10.1529\/biophysj.104.046813_bib28","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/S0168-9525(00)89161-1","article-title":"Genetic susceptibility to Alzheimer disease","volume":"11","author":"Pericak-Vance","year":"1995","journal-title":"Trends Genet."},{"key":"10.1529\/biophysj.104.046813_bib29","doi-asserted-by":"crossref","first-page":"36758","DOI":"10.1074\/jbc.M005565200","article-title":"Self-association of human apolipoprotein E3 and E4 in the presence and absence of phospholipid","volume":"275","author":"Perugini","year":"2000","journal-title":"J. Biol. Chem."},{"key":"10.1529\/biophysj.104.046813_bib30","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1056\/NEJM199511093331902","article-title":"Apolipoprotein E, dementia, and cortical deposition of beta-amyloid protein","volume":"333","author":"Polvikoski","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"10.1529\/biophysj.104.046813_bib31","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1021\/bi00504a006","article-title":"Estimation of globular protein secondary structure from circular dichroism","volume":"20","author":"Provencher","year":"1981","journal-title":"Biochemistry"},{"key":"10.1529\/biophysj.104.046813_bib32","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1194\/jlr.R300007-JLR200","article-title":"Cholesterol: from heart attacks to Alzheimer\u2019s disease","volume":"44","author":"Raffai","year":"2003","journal-title":"J. Lipid Res."},{"key":"10.1529\/biophysj.104.046813_bib33","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1021\/bi961876e","article-title":"Truncation of the amino terminus of human apolipoprotein A-I substantially alters only the lipid-free conformation","volume":"36","author":"Rogers","year":"1997","journal-title":"Biochemistry"},{"key":"10.1529\/biophysj.104.046813_bib34","doi-asserted-by":"crossref","first-page":"40949","DOI":"10.1074\/jbc.M106337200","article-title":"Lipid binding-induced conformational change in human apolipoprotein E. Evidence for two lipid-bound states on spherical particles","volume":"276","author":"Saito","year":"2001","journal-title":"J. Biol. Chem."},{"key":"10.1529\/biophysj.104.046813_bib35","doi-asserted-by":"crossref","first-page":"40723","DOI":"10.1074\/jbc.M304814200","article-title":"Effects of polymorphism on the lipid interaction of human apolipoprotein E","volume":"278","author":"Saito","year":"2003","journal-title":"J. Biol. Chem."},{"key":"10.1529\/biophysj.104.046813_bib36","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1172\/JCI117407","article-title":"Apolipoprotein E associates with beta amyloid peptide of Alzheimer\u2019s disease to form novel monofibrils. Isoform apoE4 associates more efficiently than apoE3","volume":"94","author":"Sanan","year":"1994","journal-title":"J. Clin. Invest."},{"key":"10.1529\/biophysj.104.046813_bib37","doi-asserted-by":"crossref","first-page":"5560","DOI":"10.1021\/bi963133z","article-title":"Nonsequential unfolding of the alpha\/beta barrel protein indole-3-glycerol-phosphate synthase","volume":"36","author":"S\u00e1nchez del Pino","year":"1997","journal-title":"Biochemistry"},{"key":"10.1529\/biophysj.104.046813_bib38","doi-asserted-by":"crossref","first-page":"8552","DOI":"10.1073\/pnas.92.19.8552","article-title":"Genetic dissection of Alzheimer disease, a heterogeneous disorder","volume":"92","author":"Schellenberg","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"10.1529\/biophysj.104.046813_bib39","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1016\/S0006-3495(98)74069-X","article-title":"Sedimentation analysis of noninteracting and self-associating solutes using numerical solutions to the Lamm equation","volume":"75","author":"Schuck","year":"1998","journal-title":"Biophys. J."},{"key":"10.1529\/biophysj.104.046813_bib40","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1016\/S0006-3495(00)76713-0","article-title":"Size-distribution analysis of macromolecules by sedimentation velocity ultracentrifugation and Lamm equation modeling","volume":"78","author":"Schuck","year":"2000","journal-title":"Biophys. J."},{"key":"10.1529\/biophysj.104.046813_bib41","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/S0003-2697(03)00289-6","article-title":"On the analysis of protein self-association by sedimentation velocity analytical ultracentrifugation","volume":"320","author":"Schuck","year":"2003","journal-title":"Anal. Biochem."},{"key":"10.1529\/biophysj.104.046813_bib42","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1016\/S0006-3495(02)75469-6","article-title":"Size-distribution analysis of proteins by analytical ultracentrifugation: strategies and application to model systems","volume":"82","author":"Schuck","year":"2002","journal-title":"Biophys. J."},{"key":"10.1529\/biophysj.104.046813_bib43","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1152\/physrev.2001.81.2.741","article-title":"Alzheimer\u2019s disease: genes, proteins, and therapy","volume":"81","author":"Selkoe","year":"2001","journal-title":"Physiol. Rev."},{"key":"10.1529\/biophysj.104.046813_bib44","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1002\/bip.360310111","article-title":"Study of the \u201cmolten globule\u201d intermediate state in protein folding by a hydrophobic fluorescent probe","volume":"31","author":"Semisotnov","year":"1991","journal-title":"Biopolymers"},{"key":"10.1529\/biophysj.104.046813_bib45","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1093\/clinchem\/41.8.1068","article-title":"Apolipoprotein E: an important gene and protein to follow in laboratory medicine","volume":"41","author":"Siest","year":"1995","journal-title":"Clin. Chem."},{"key":"10.1529\/biophysj.104.046813_bib46","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.1016\/S0006-3495(01)75838-9","article-title":"Non-ideality by sedimentation velocity of halophilic malate dehydrogenase in complex solvents","volume":"81","author":"Solovyova","year":"2001","journal-title":"Biophys. J."},{"key":"10.1529\/biophysj.104.046813_bib47","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1110\/ps.8.2.370","article-title":"Estimation of the number of helical and strand segments in proteins using CD spectroscopy","volume":"8","author":"Sreerama","year":"1999","journal-title":"Protein Sci."},{"key":"10.1529\/biophysj.104.046813_bib48","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1006\/abio.1993.1079","article-title":"A self-consistent method for the analysis of protein secondary structure from circular dichroism","volume":"209","author":"Sreerama","year":"1993","journal-title":"Anal. Biochem."},{"key":"10.1529\/biophysj.104.046813_bib49","doi-asserted-by":"crossref","first-page":"4725","DOI":"10.1073\/pnas.92.11.4725","article-title":"Apolipoprotein E and Alzheimer disease","volume":"92","author":"Strittmatter","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1529\/biophysj.104.046813_bib50","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/0021-9150(94)90204-6","article-title":"Apolipoprotein epsilon 4 homozygosity: a determinant of restenosis after coronary angioplasty","volume":"110","author":"Van Bockxmeer","year":"1994","journal-title":"Atherosclerosis"},{"key":"10.1529\/biophysj.104.046813_bib51","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/0003-2697(90)90396-Q","article-title":"Estimation of protein secondary structure and error analysis from CD spectra","volume":"191","author":"Van Stokkum","year":"1990","journal-title":"Anal. Biochem."},{"key":"10.1529\/biophysj.104.046813_bib52","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0065-3233(08)60642-7","article-title":"Apolipoprotein E: structure-function relationships","volume":"45","author":"Weisgraber","year":"1994","journal-title":"Adv. Protein Chem."},{"key":"10.1529\/biophysj.104.046813_bib53","doi-asserted-by":"crossref","first-page":"15745","DOI":"10.1016\/S0021-9258(18)82318-3","article-title":"Discrete carboxyl-terminal segments of apolipoprotein E mediate lipoprotein association and protein oligomerization","volume":"268","author":"Westerlund","year":"1993","journal-title":"J. Biol. Chem."},{"key":"10.1529\/biophysj.104.046813_bib54","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1126\/science.2063194","article-title":"Three-dimensional structure of the LDL receptor-binding domain of human apolipoprotein E","volume":"252","author":"Wilson","year":"1991","journal-title":"Science"}],"container-title":["Biophysical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006349505731209?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006349505731209?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T16:18:18Z","timestamp":1762100298000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0006349505731209"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,1]]},"references-count":54,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2005,1]]}},"alternative-id":["S0006349505731209"],"URL":"https:\/\/doi.org\/10.1529\/biophysj.104.046813","relation":{},"ISSN":["0006-3495"],"issn-type":[{"value":"0006-3495","type":"print"}],"subject":[],"published":{"date-parts":[[2005,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Structural Variation in Human Apolipoprotein E3 and E4: Secondary Structure, Tertiary Structure, and Size Distribution","name":"articletitle","label":"Article Title"},{"value":"Biophysical Journal","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1529\/biophysj.104.046813","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2005 The Biophysical Society. Published by Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}