{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T13:50:59Z","timestamp":1754488259139},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"S1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Syst Biol"],"published-print":{"date-parts":[[2013,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>We explore whether the process of multimerization can be used as a means to regulate noise in the abundance of functional protein complexes. Additionally, we analyze how this process affects the mean level of these functional units, response time of a gene, and temporal correlation between the numbers of expressed proteins and of the functional multimers. We show that, although multimerization increases noise by reducing the mean number of functional complexes it can reduce noise in comparison with a monomer, when abundance of the functional proteins are comparable. Alternatively, reduction in noise occurs if both monomeric and multimeric forms of the protein are functional. Moreover, we find that multimerization either increases the response time to external signals or decreases the correlation between number of functional complexes and protein production kinetics. Finally, we show that the results are in agreement with recent genome-wide assessments of cell-to-cell variability in protein numbers and of multimerization in essential and non-essential genes in <jats:italic>Escherichia coli<\/jats:italic>, and that the effects of multimerization are tangible at the level of genetic circuits.<\/jats:p>","DOI":"10.1186\/1752-0509-7-s1-s3","type":"journal-article","created":{"date-parts":[[2013,8,12]],"date-time":"2013-08-12T10:14:56Z","timestamp":1376302496000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Effects of multimerization on the temporal variability of protein complex abundance"],"prefix":"10.1186","volume":"7","author":[{"given":"Antti","family":"H\u00e4kkinen","sequence":"first","affiliation":[]},{"given":"Huy","family":"Tran","sequence":"additional","affiliation":[]},{"given":"Olli","family":"Yli-Harja","sequence":"additional","affiliation":[]},{"given":"Brian","family":"Ingalls","sequence":"additional","affiliation":[]},{"given":"Andre S","family":"Ribeiro","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2013,8,12]]},"reference":[{"key":"1126_CR1","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1146\/annurev.bi.54.070185.001131","volume":"54","author":"WR McClure","year":"1985","unstructured":"McClure WR: Mechanism and control of transcription initiation in prokaryotes. Annu Rev Biochem. 1985, 54: 171-204. 10.1146\/annurev.bi.54.070185.001131.","journal-title":"Annu Rev Biochem"},{"issue":"18","key":"1126_CR2","doi-asserted-by":"publisher","first-page":"3873","DOI":"10.1093\/nar\/29.18.3873","volume":"29","author":"R Lutz","year":"2001","unstructured":"Lutz R, Lozinski T, Ellinger T, Bujard H: Dissecting the functional program of Escherichia coli promoters: The combined mode of action of Lac repressor and AraC activator. Nucleic Acids Res. 2001, 29 (18): 3873-3881. 10.1093\/nar\/29.18.3873.","journal-title":"Nucleic Acids Res"},{"issue":"6","key":"1126_CR3","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.1042\/BST0341062","volume":"34","author":"R Landick","year":"2006","unstructured":"Landick R: The regulatory roles and mechanism of transcriptional pausing. Biochem Soc Trans. 2006, 34 (6): 1062-1066.","journal-title":"Biochem Soc Trans"},{"issue":"3","key":"1126_CR4","doi-asserted-by":"publisher","first-page":"e1000704","DOI":"10.1371\/journal.pcbi.1000704","volume":"6","author":"T Rajala","year":"2010","unstructured":"Rajala T, Hakkinen A, Healy S, Yli-Harja O, Ribeiro AS: Effects of transcriptional pausing on gene expression dynamics. PLoS Comput Biol. 2010, 6 (3): e1000704-10.1371\/journal.pcbi.1000704.","journal-title":"PLoS Comput Biol"},{"issue":"12","key":"1126_CR5","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1016\/S0968-0004(02)02207-7","volume":"27","author":"CI Holberg","year":"2002","unstructured":"Holberg CI, Tran SEF, Eriksson JE, Sistonen L: Multisite phosphorylation provides sophisticated regulation of transcription factors. Trends Biochem Sci. 2002, 27 (12): 619-627. 10.1016\/S0968-0004(02)02207-7.","journal-title":"Trends Biochem Sci"},{"issue":"5991","key":"1126_CR6","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1126\/science.1188308","volume":"329","author":"Y Taniguchi","year":"2010","unstructured":"Taniguchi Y, Choi PJ, Li GW, Chen H, Babu M, Hearn J, Emili A, Xie XS: Quantifying E. coli proteome and transcriptome with single-molecule sensitivity in single cells. Science. 2010, 329 (5991): 533-538. 10.1126\/science.1188308.","journal-title":"Science"},{"issue":"5","key":"1126_CR7","doi-asserted-by":"publisher","first-page":"3607","DOI":"10.1074\/jbc.M110.167254","volume":"286","author":"JN Ollivierre","year":"2011","unstructured":"Ollivierre JN, Sikora JL, Beuning PJ: The dimeric SOS mutagenesis protein UmuD is active as a monomer. J Biol Chem. 2011, 286 (5): 3607-3617. 10.1074\/jbc.M110.167254.","journal-title":"J Biol Chem"},{"issue":"17","key":"1126_CR8","doi-asserted-by":"publisher","first-page":"6528","DOI":"10.1073\/pnas.86.17.6528","volume":"89","author":"A Escher","year":"1989","unstructured":"Escher A, O'Kane DJ, Lee J, Szalay AA: Bacterial luciferase alpha beta fusion protein is fully active as a monomer and highly sensitive in vivo to elevated temperature. Proc Natl Acad Sci USA. 1989, 89 (17): 6528-6532.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"5","key":"1126_CR9","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1021\/bi061636r","volume":"46","author":"B D'Autreaux","year":"2007","unstructured":"D'Autreaux B, Pecqueur L, Gonzalez de Peredo A, Diederix REM, Caux-Thang C, Tabet L, Bersch B, Forest E, Michaud-Soret I: Reversible Redox- and Zinc-dependent dimerization of the Escherichia coli Fur protein. Biochemistry. 2007, 46 (5): 1329-1342. 10.1021\/bi061636r.","journal-title":"Biochemistry"},{"issue":"6","key":"1126_CR10","doi-asserted-by":"publisher","first-page":"061903","DOI":"10.1103\/PhysRevE.75.061903","volume":"75","author":"AS Ribeiro","year":"2007","unstructured":"Ribeiro AS: Effects of coupling strength and space on the dynamics of coupled toggle switches in stochastic gene networks with multiple-delayed reactions. Phys Rev E. 2007, 75 (6): 061903-","journal-title":"Phys Rev E"},{"issue":"5","key":"1126_CR11","doi-asserted-by":"publisher","first-page":"051915","DOI":"10.1103\/PhysRevE.76.051915","volume":"76","author":"AS Ribeiro","year":"2007","unstructured":"Ribeiro AS: Dynamics of a two-dimensional model of cell tissues with coupled stochastic gene networks. Phys Rev E. 2007, 76 (5): 051915-","journal-title":"Phys Rev E"},{"issue":"18","key":"1126_CR12","doi-asserted-by":"publisher","first-page":"188101","DOI":"10.1103\/PhysRevLett.96.188101","volume":"96","author":"A Lipshtat","year":"2006","unstructured":"Lipshtat A, Loinger A, Balaban NQ, Biham O: Genetic toggle switch without cooperative binding. Phys Rev Lett. 2006, 96 (18): 188101-","journal-title":"Phys Rev Lett"},{"key":"1126_CR13","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1186\/1752-0509-5-149","volume":"5","author":"M Kandhavelu","year":"2011","unstructured":"Kandhavelu M, Mannerstrom H, Gupta A, Hakkinen A, Lloyd-Price J, Yli-Harja O, Ribeiro AS: In vivo kinetics of transcription initiation of the lar promoter in Escherichia coli: Evidence for a sequential mechanism with two rate-limiting steps. BMC Syst Biol. 2011, 5: 149-10.1186\/1752-0509-5-149.","journal-title":"BMC Syst Biol"},{"issue":"17","key":"1126_CR14","doi-asserted-by":"publisher","first-page":"8472","DOI":"10.1093\/nar\/gks583","volume":"40","author":"AB Muthukrishnan","year":"2012","unstructured":"Muthukrishnan AB, Kandhavelu M, Lloyd-Price J, Kudasov F, Chowdhury S, Yli-Harja O, Ribeiro AS: Dynamics of transcription driven by the tetA promoter, one event at a tive, in live Escherichia coli cells. Nucleic Acids Res. 2012, 40 (17): 8472-8483. 10.1093\/nar\/gks583.","journal-title":"Nucleic Acids Res"},{"issue":"6","key":"1126_CR15","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1038\/nrg1615","volume":"6","author":"M Kaern","year":"2005","unstructured":"Kaern M, Elston TC, Blake WJ, Collins JJ: Stochasticity in gene expression: From theories to phenotypes. Nat Rev Genet. 2005, 6 (6): 451-464. 10.1038\/nrg1615.","journal-title":"Nat Rev Genet"},{"issue":"9","key":"1126_CR16","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1089\/cmb.2006.13.1630","volume":"13","author":"AS Ribeiro","year":"2006","unstructured":"Ribeiro AS, Zhu R, Kauffman SA: A general modeling strategy for gene regulatory networks with stochastic dynamics. J Comp Biol. 2006, 13 (9): 1630-1639. 10.1089\/cmb.2006.13.1630.","journal-title":"J Comp Biol"},{"issue":"4","key":"1126_CR17","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1088\/1478-3975\/3\/4\/005","volume":"3","author":"MR Roussel","year":"2006","unstructured":"Roussel MR, Zhu R: Validation of an algorithm for delay stochastic simulation of transcription and translation in prokaryotic gene expression title. Phys Biol. 2006, 3 (4): 274-284. 10.1088\/1478-3975\/3\/4\/005.","journal-title":"Phys Biol"},{"issue":"25","key":"1126_CR18","doi-asserted-by":"publisher","first-page":"2340","DOI":"10.1021\/j100540a008","volume":"81","author":"DT Gillespie","year":"1977","unstructured":"Gillespie DT: Exact stochastic simulation of coupled chemical reactions. J Phys Chem. 1977, 81 (25): 2340-2361. 10.1021\/j100540a008.","journal-title":"J Phys Chem"},{"issue":"12","key":"1126_CR19","doi-asserted-by":"crossref","first-page":"3019","DOI":"10.1128\/JB.180.12.3019-3025.1998","volume":"180","author":"PL deHaseth","year":"1998","unstructured":"deHaseth PL, Zupancic ML, Record MT: RNA polymerase-promoter interactions: the comings and goings of RNA polymerase. J Bacteriol. 1998, 180 (12): 3019-3025.","journal-title":"J Bacteriol"},{"issue":"2","key":"1126_CR20","doi-asserted-by":"publisher","first-page":"026004","DOI":"10.1088\/1478-3975\/9\/2\/026004","volume":"9","author":"M Kandhavelu","year":"2012","unstructured":"Kandhavelu M, Hakkinen A, Yli-Harja O, Ribeiro AS: Single-molecule dynamics of transcription of the lar promoter. Phys Biol. 2012, 9 (2): 026004-10.1088\/1478-3975\/9\/2\/026004.","journal-title":"Phys Biol"},{"issue":"6","key":"1126_CR21","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1016\/j.cell.2006.04.032","volume":"125","author":"KM Herbert","year":"2006","unstructured":"Herbert KM, La Porta A, Wong BJ, Mooney RA, Neuman KC, Landick R, Block SM: Sequence-resolved detection of pausing by single RNA polymerase molecules. Cell. 2006, 125 (6): 1083-1094. 10.1016\/j.cell.2006.04.032.","journal-title":"Cell"},{"issue":"6","key":"1126_CR22","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1016\/j.cell.2005.09.031","volume":"123","author":"I Golding","year":"2005","unstructured":"Golding I, Paulsson J, Zawilski SM, Cox EC: Real-time kinetics of gene activity in individual bacteria. Cell. 2005, 123 (6): 1025-1036. 10.1016\/j.cell.2005.09.031.","journal-title":"Cell"},{"issue":"3943","key":"1126_CR23","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1126\/science.169.3943.392","volume":"169","author":"OL Miller Jr","year":"1970","unstructured":"Miller OL, Hamkalo BA, Thomas CA: Visualization of bacterial genes in action. Science. 1970, 169 (3943): 392-395. 10.1126\/science.169.3943.392.","journal-title":"Science"},{"issue":"5495","key":"1126_CR24","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1038\/254034a0","volume":"254","author":"J Shine","year":"1975","unstructured":"Shine J, Dalgarno L: Determinant of cistron specificity in bacterial ribosomes. Nature. 1975, 254 (5495): 34-38. 10.1038\/254034a0.","journal-title":"Nature"},{"issue":"15","key":"1126_CR25","doi-asserted-by":"publisher","first-page":"9697","DOI":"10.1073\/pnas.112318199","volume":"99","author":"JA Bernstein","year":"2002","unstructured":"Bernstein JA, Khodursky AB, Lin PH, Lin-Chao S, Cohen SN: Global analysis of mRNA decay and abundance in Escherichia coli at single-gene resolution using two-color fluorescent DNA microarrays. Proc Natl Acad Sci USA. 2002, 99 (15): 9697-9702. 10.1073\/pnas.112318199.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"2","key":"1126_CR26","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1006\/tpbi.1995.1027","volume":"48","author":"J Peccoud","year":"1995","unstructured":"Peccoud J, Ycart B: Markovian modelling of gene product synthesis. Theor Popul Biol. 1995, 48 (2): 222-234. 10.1006\/tpbi.1995.1027.","journal-title":"Theor Popul Biol"},{"issue":"5767","key":"1126_CR27","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1126\/science.1119623","volume":"311","author":"J Yu","year":"2006","unstructured":"Yu J, Xiao J, Ren X, Lao K, Xie XS: Probing gene expression in live cells, one protein molecule at a time. Science. 2006, 311 (5767): 1600-1603. 10.1126\/science.1119623.","journal-title":"Science"},{"key":"1126_CR28","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1186\/1471-2105-12-121","volume":"12","author":"J Makela","year":"2011","unstructured":"Makela J, Lloyd-Price J, Yli-Harja O, Ribeiro AS: Stochastic sequence-level model of coupled transcription and translation in prokaryotes. BMC Bioinf. 2011, 12: 121-10.1186\/1471-2105-12-121.","journal-title":"BMC Bioinf"},{"key":"1126_CR29","doi-asserted-by":"crossref","first-page":"6956","DOI":"10.1016\/S0021-9258(19)45938-3","volume":"246","author":"K Nath","year":"1971","unstructured":"Nath K, Koch A: Protein degradation in Escherichia coli. J Biol Chem. 1971, 246: 6956-6967.","journal-title":"J Biol Chem"},{"issue":"6767","key":"1126_CR30","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1038\/35002131","volume":"403","author":"TS Gardner","year":"2000","unstructured":"Gardner TS, Cantor CR, Collins JJ: Construction of a genetic toggle switch in Escherichia coli. Nature. 2000, 403 (6767): 339-342. 10.1038\/35002131.","journal-title":"Nature"},{"issue":"22","key":"1126_CR31","doi-asserted-by":"publisher","first-page":"3004","DOI":"10.1093\/bioinformatics\/bts556","volume":"28","author":"J Lloyd-Price","year":"2012","unstructured":"Lloyd-Price J, Gupta A, Ribeiro AS: SGNS2: A compartmentalized stochastic chemical kinetics simulator for dynamic cell populations. Bioinf. 2012, 28 (22): 3004-3005. 10.1093\/bioinformatics\/bts556.","journal-title":"Bioinf"},{"issue":"5861","key":"1126_CR32","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1126\/science.1144331","volume":"319","author":"JM Pedraza","year":"2008","unstructured":"Pedraza JM, Paulsson J: Effects of molecular memory and bursting on fluctuations in gene expression. Science. 2008, 319 (5861): 339-343. 10.1126\/science.1144331.","journal-title":"Science"}],"container-title":["BMC Systems Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1752-0509-7-S1-S3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T00:58:44Z","timestamp":1630544324000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcsystbiol.biomedcentral.com\/articles\/10.1186\/1752-0509-7-S1-S3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,8]]},"references-count":32,"journal-issue":{"issue":"S1","published-print":{"date-parts":[[2013,8]]}},"alternative-id":["1126"],"URL":"https:\/\/doi.org\/10.1186\/1752-0509-7-s1-s3","relation":{},"ISSN":["1752-0509"],"issn-type":[{"value":"1752-0509","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,8]]},"assertion":[{"value":"12 August 2013","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"S3"}}