Fernando de la Cruz Calahorra (IP)

  • fernando.cruz@unican.es
  • 942 201942
  • Intergenomics
  • Principal Investigator
  • Microbiology & Genomics
  • Department of Microbiology & Genomics

The Intergenomics Group is composed of around 20 researchers with a common general research focus on plasmid biology and, more specifically, the mechanism of bacterial conjugation. Among the members of the group there are experts in microbiology, bacterial genetics, protein engineering, protein purification, crystallography, electron microscopy and biocatalysis. This makes the Intergenomics group a powerful team that can work independently or in cooperation with other research groups.

Intergenomics


Research lines

– Evolution and Ecology:

         • Classification of conjugative and mobilizable plasmids based on their relaxase sequences.

         • Conjugative systems of Cyanobacteria and Actinomycetes.  

– Molecular Engines: Protein and DNA transporters across bacterial membranes

– Protein Engineering: Conjugative relaxases as a target for the inhibition of the dissemination of antibiotic resistance.

– Systems Biology


Funding


- Nuevas estrategias para el control de infecciones nosocomiales. INNOECO RTC-2015-3184-1. 

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​ ​“Promover el desarrollo tecnológico, la innovación y una investigación de calidad”


- Plásmidos ortogonales para Biología Sintética y de Sistemas. Ministerio de Educación (BFU2011-26608).

Bacterial Computing with Engineered Populations (BACTOCOM). European Union 7th Framework. Programme, Area Information and Communication Technologies (FP7-ICT-2009-4; Proyecto nº 248919).

- EVOTAR: Evolution and transfer of antibiotic resistance (Project no. 282004). European Union FP7-HEALTH 2011.2.3.1-2.

- Diversidad y distribución de plásmidos de bacterias ácido-lácticas. Acción Integrada Hispano-Serbia. PRI-AIBSE-2011-1186. IP: Fernando de la Cruz

- INGENIERÍA GENÉTICA DE ESCHERICHIA COLI PARA MEJORAR LA PRODUCCIÓN DE LÍPIDOS RICOS EN ÁCIDOS GRASOS OMEGA-3 (TF16-XX-003), cofinanciado por SODERCAN S.A. y el Programa Operativo FEDER



Integrated strategy for the separation of endotoxins from biofluids. LPS capture on newly synthesized protein

Integrated strategy for the separation of endotoxins from biofluids. LPS capture on newly synthesized protein

Basauri A., Fallanza M., Giner-Robles L., Fernandez-Lopez R., Moncalián G., de la Cruz F., Ortiz I.

Separation and Purification Technology. Volume 255, 15 January 2021, 117689



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Pathways for horizontal gene transfer in bacteria revealed by a global map of their plasmids

Santiago Redondo-Salvo, Raúl Fernández-López, Raúl Ruiz, Luis Vielva, María de Toro, Eduardo P C Rocha, M Pilar Garcillán-Barcia, Fernando de la Cruz

​Nat Commun. 2020 Jul 17;11(1):3602. doi: 10.1038/s41467-020-17278-2.


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Biochemical interactions between LPS and LPS-binding molecules

Basauri A, González-Fernández C, Fallanza M, Bringas E, Fernandez-Lopez R, Giner L, Moncalián G, de la Cruz F, Ortiz I.

​Crit Rev Biotechnol. 2020 May;40(3):292-305. doi: 10.1080/07388551.2019.1709797. Epub 2020 Jan 13.

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ArdC, a ssDNA-binding protein with a metalloprotease domain, overpasses the recipient hsdRMS restriction system broadening conjugation host range

Lorena González-Montes, Irene Del Campo, M Pilar Garcillán-Barcia, Fernando de la Cruz, Gabriel Moncalián

​PLoS Genet. 2020 Apr 29;16(4):e1008750. doi: 10.1371/journal.pgen.1008750. eCollection 2020 Apr.


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fabH deletion increases DHA production in Escherichia coli expressing Pfa genes.

Giner-Robles, L.; Lázaro, B.; de la Cruz, F. and Moncalián, G.

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Heterologous Expression of a Thermophilic Diacylglycerol Acyltransferase Triggers Triglyceride Accumulation in Escherichia coli.

Lázaro, B.; Villa, J.A.; Santín, O.; Cabezas, M.; Milagre, C.D.F.; de la Cruz, F. and Moncalián, G.

​Plos One. 12(4):e0176520. doi: 10.1371/journal.pone.0176520. 

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Conjugation Inhibitors and Their Potential Use to Prevent Dissemination of Antibiotic Resistance Genes in Bacteria

Conjugation Inhibitors and Their Potential Use to Prevent Dissemination of Antibiotic Resistance Genes in Bacteria

Cabezón E, de la Cruz F, Arechaga I.

​Front Microbiol. 2017 Nov 30;8:2329. doi: 10.3389/fmicb.2017.02329. eCollection 2017.

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Nutrient starvation leading to triglyceride accumulation activates the Entner Doudoroff pathway in Rhodococcus jostii RHA1.

Juárez A, Villa JA, Lanza VF, Lázaro B, de la Cruz F, Álvarez HM and Moncalián G.

Microbial Cell Factories 16,35. doi: 10.1186/s12934-017-0651-7.

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Relaxosomes and plasmid transfer in Gram-negative bacteria.

Zechner, E.L.; Moncalián, G. and de la Cruz, F.

Current Topics in Microbiology and Immunology. 413:93-113. doi: 10.1007/978-3-319-75241-9_4.

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Substrate translocation involves specific lysine residues of the central channel of the conjugative coupling protein TrwB.

Larrea D, de Paz HD, Matilla I, Guzmán-Herrador DL, Lasso G, de la Cruz F, Cabezón E, Llosa M. ol Genet Genomics. 2017 Jun 8. doi: 10.1007/s00438-017-1331-3. (Epub ahead of print)

[pubmed]

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Design of Novel Relaxase Substrates Based on Rolling Circle Replicases for Bioconjugation to DNA Nanostructures.

Sagredo S, de la Cruz F and Moncalián G.

PLoS One;11:e0152666. doi:0.1371/journal.pone.0152666.

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Orthogonal protein assembly on DNA nanostructures using relaxases.

Sagredo,S., Pirzer,T., Rafat, A.A., Goetzfried,M.A., Moncalian, G., Simmel, F.C. and de la Cruz, F.

Sagredo,S., Pirzer,T., Rafat, A.A., Goetzfried,M.A., Moncalian, G., Simmel, F.C. and de la Cruz, F. (2016b).  Orthogonal protein assembly on DNA nanostructures using relaxases. Angewandte Chemie Int. Ed. 55, 4348-52. doi: 10.1002/anie.201510313. IF 11.994. D1 (13/166)

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Comparative genomics of the conjugation region of F-like plasmids: five shades of F.

Fernandez Lopez R, De Toro Hernando M, Moncalian G, Garcillán-Barcia MP and de la Cruz F

Fernandez Lopez R, De Toro Hernando M, Moncalian G, Garcillán-Barcia MP and de la Cruz F (2016) Comparative genomics of the conjugation region of F-like plasmids: five shades of F. Front Mol Biosci. doi: 10.3389/fmolb.2016.00071

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Concerted action of NIC relaxase and auxiliary protein MobC in RA3 plasmid conjugation.

Godziszewska J, Moncalián G, Cabezas M, Bartosik AA, de la Cruz F, Jagura-Burdzy G. Mol Microbiol. 2016 Aug;101(3):439-56. doi: 10.1111/mmi.13401. Epub 2016 Jun 2.

[PubMed]

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Concerted action of NIC relaxase and auxiliary protein MobC in RA3 plasmid conjugation.

Godziszewska J, Moncalián G, Cabezas M, Bartosik AA, de la Cruz F and Jagura-Burdzy G.

Godziszewska J, Moncalián G, Cabezas M, Bartosik AA, de la Cruz F and Jagura-Burdzy G. (2016). Concerted action of NIC relaxase and auxiliary protein MobC in RA3 plasmid conjugation. Mol Microbiol. doi: 10.1111/mmi.13401.

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Genomics of high molecular weight plasmids isolated from an on-farm biopurification system.

Martini MC, Wibberg D, Lozano M, Torres Tejerizo G, Albicoro FJ, Jaenicke S, van Elsas JD, Petroni A, Garcillán-Barcia MP, de la Cruz F, Schlüter A, Pühler A, Pistorio M, Lagares A, Del Papa MF. Sci Rep. 2016 Jun 20;6:28284. doi: 10.1038/srep28284.

[PubMed]

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Type IV traffic ATPase TrwD as molecular target to inhibit bacterial conjugation.

Ripoll-Rozada J, García-Cazorla Y, Getino M, Machón C, Sanabria-Ríos D, de la Cruz F, Cabezón E, Arechaga I. Mol Microbiol. 2016 Jun;100(5):912-21. doi: 10.1111/mmi.13359.

[pubmed]

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Type IV traffic ATPase TrwD as molecular target to inhibit bacterial conjugation.

Ripoll-Rozada J, García-Cazorla Y, Getino M, Machón C, Sanabria-Ríos D, de la Cruz F, Cabezón E, Arechaga I. Mol Microbiol. 2016 Jun;100(5):912-21. doi: 10.1111/mmi.13359. Epub 2016 Mar 22.

[PubMed]

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Transcription factor-based biosensors enlightened by the analyte.

Fernández-López R, Ruiz R, de la Cruz F, Moncalián G.

Fernández-López R, Ruiz R, de la Cruz F, Moncalián G. (2015) Transcription factor-based biosensors enlightened by the analyte. Front Microbiol. 6:648. doi: 10.3389/fmicb.2015.00648. 

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Rebooting the genome: The role of negative feedback in horizontal gene transfer.

Fernandez-Lopez R, de la Cruz F. Mob Genet Elements. 2015 Feb 23;4(6):1-6. eCollection 2014 Nov-Dec.

[PubMed]

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Degenerate primer MOB typing of multiresistant clinical isolates of E. coli uncovers new plasmid backbones.

Garcillán-Barcia MP, Ruiz Del Castillo B, Alvarado A, de la Cruz F, Martínez-Martínez L. Plasmid. 2015 Jan;77:17-27. doi: 10.1016/j.plasmid.2014.11.003.

[pubmed]

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Towards an integrated model of bacterial conjugation.

Cabezón E, Ripoll-Rozada J, Peña A, de la Cruz F, Arechaga I. FEMS Microbiol Rev. Vol.39:81-95. doi: 10.1111/1574-6976.12085.

 [pubmed]

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Dissemination of Cephalosporin Resistance Genes between Escherichia coli Strains from Farm Animals and Humans by Specific Plasmid Lineages.

de Been M, Lanza VF, de Toro M, Scharringa J, Dohmen W, Du Y, Hu J, Lei Y, Li N, Tooming-Klunderud A, Heederik DJ, Fluit AC, Bonten MJ, Willems RJ, de la Cruz F, van Schaik W. PLoS Genet. 2014 Dec 18;10(12):e1004776. doi: 10.1371/journal.pgen.1004776.

[pubmed]

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Plasmid Flux in Escherichia coli ST131 Sublineages, Analyzed by Plasmid Constellation Network (PLACNET), a New Method for Plasmid Reconstruction from Whole Genome Sequences.

Lanza VF, de Toro M, Garcillán-Barcia MP, Mora A, Blanco J, Coque TM, de la Cruz F. PLoS Genet. 2014 Dec 18;10(12):e1004766. doi: 10.1371/journal.pgen.1004766.

[pubmed]

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Molecular epidemiology and virulence of Escherichia coli O16:H5-ST131: comparison with H30 and H30-Rx subclones of O25b:H4-ST131.

Dahbi G, Mora A, Mamani R, López C, Alonso MP, Marzoa J, Blanco M, Herrera A, Viso S, García-Garrote F, Tchesnokova V, Billig M, de la Cruz F, de Toro M, González-López JJ, Prats G, Chaves F, Martínez-Martínez L, López-Cerezo L, Denamur E, Blanco J. Int J

[pubmed]

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A high security double lock and key mechanism in HUH relaxases controls oriT-processing for plasmid conjugation.

Carballeira JD, González-Pérez B, Moncalián G, de la Cruz F. Nucleic Acids Res. 2014;42(16):10632-43. doi: 10.1093/nar/gku741.

[pubmed]

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PipX, the coactivator of NtcA, is a global regulator in cyanobacteria.

Espinosa J, Rodríguez-Mateos F, Salinas P, Lanza VF, Dixon R, de la Cruz F, Contreras A. Proc Natl Acad Sci U S A. 2014 Jun 10;111(23):E2423-30. doi: 10.1073/pnas.1404097111.

[pubmed]

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Key components of the eight classes of type IV secretion systems involved in bacterial conjugation or protein secretion.

Guglielmini J, Néron B, Abby SS, Garcillán-Barcia MP, de la Cruz F, Rocha EP. Nucleic Acids Res. 2014;42(9):5715-27. doi: 10.1093/nar/gku194.

[pubmed]

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Plasmid conjugation from proteobacteria as evidence for the origin of xenologous genes in cyanobacteria.

Encinas D, Garcillán-Barcia MP, Santos-Merino M, Delaye L, Moya A, de la Cruz F. J Bacteriol. 2014 Apr;196(8):1551-9. doi: 10.1128/JB.01464-13.

[pubmed]

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Negative feedback and transcriptional overshooting in a regulatory network for horizontal gene transfer.

Fernandez-Lopez R, Del Campo I, Revilla C, Cuevas A, de la Cruz F. PLoS Genet. 2014 Feb 27;10(2):e1004171. doi: 10.1371/journal.pgen.1004171.

[pubmed]

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Use of limited proteolysis and mutagenesis to identify folding domains and sequence motifs critical for wax ester synthase/acyl coenzyme A:diacylglycerol acyltransferase activity.

Villa JA, Cabezas M, de la Cruz F, Moncalián G. Appl Environ Microbiol. 2014 Feb;80(3):1132-41. doi: 10.1128/AEM.03433-13.

[pubmed]

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Use of limited proteolysis and mutagenesis to identify folding domains and sequence motifs critical for wax ester synthase/acyl coenzyme A:diacylglycerol acyltransferase activity.

Villa JA, Cabezas M, de la Cruz F, Moncalián G. Appl Environ Microbiol. 2014 Feb;80(3):1132-41. doi: 10.1128/AEM.03433-13.

[pubmed]

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Genomic analysis of the emergence and evolution of multidrug resistance during a Klebsiella pneumoniae outbreak including carbapenem and colistin resistance.

López-Camacho E, Gómez-Gil R, Tobes R, Manrique M, Lorenzo M, Galván B, Salvarelli E, Moatassim Y, Salanueva IJ, Pareja E, Codoñer FM, Alvarez-Tejado M, Garcillán-Barcia MP, De la Cruz F, Mingorance J. J Antimicrob Chemother. 2013 Oct 23.

[pubmed]

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Four main virotypes among extended-spectrum-β-lactamase-producing isolates of Escherichia coli O25b:H4-B2-ST131: bacterial, epidemiological, and clinical characteristics.

Blanco J, Mora A, Mamani R, López C, Blanco M, Dahbi G, Herrera A, Marzoa J, Fernández V, de la Cruz F, Martínez-Martínez L, Alonso MP, Nicolas-Chanoine MH, Johnson JR, Johnston B, López-Cerero L, Pascual A, Rodríguez-Baño J; Spanish Group for Nosocomial

[pubmed]

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The transmembrane domain of the T4SS coupling protein TrwB and its role in protein-protein interactions.

Segura RL, Aguila-Arcos S, Ugarte-Uribe B, Vecino AJ, de la Cruz F, Goñi FM, Alkorta I. Biochim Biophys Acta. 2013 Sep;1828(9):2015-25. doi: 10.1016/j.bbamem.2013.05.022.

[pubmed]

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Subcellular location of the coupling protein TrwB and the role of its transmembrane domain.

Segura RL, Aguila-Arcos S, Ugarte-Uribe B, Vecino AJ, de la Cruz F, Goñi FM, Alkorta I. Biochim Biophys Acta. 2013 Sep 6;1838(1PB):223-230. doi: 10.1016/j.bbamem.2013.08.016.

[pubmed]

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Functional interactions of VirB11 traffic ATPases with VirB4 and VirD4 molecular motors in type IV secretion systems.

Ripoll-Rozada J, Zunzunegui S, de la Cruz F, Arechaga I, Cabezón E. J Bacteriol. 2013 Sep;195(18):4195-201. doi: 10.1128/JB.00437-13.

[pubmed]

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Breaking and joining single-stranded DNA: the HUH endonuclease superfamily.

Chandler M, de la Cruz F, Dyda F, Hickman AB, Moncalian G, Ton-Hoang B. Nat Rev Microbiol. 2013 Aug;11(8):525-38. doi: 10.1038/nrmicro3067.

[pubmed]

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Catalytic domain of plasmid pAD1 relaxase TraX defines a group of relaxases related to restriction endonucleases.

Francia MV, Clewell DB, de la Cruz F, Moncalián G. Proc Natl Acad Sci U S A. 2013 Aug 13;110(33):13606-11. doi: 10.1073/pnas.1310037110. Epub 2013 Jul 31.

[pubmed]

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Structural independence of conjugative coupling protein TrwB from its Type IV secretion machinery

Larrea D, de Paz HD, Arechaga I, de la Cruz F, Llosa M. Plasmid. 2013 Jul;70(1):146-53. doi: 10.1016/j.plasmid.2013.03.006.

[pubmed]

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Multicellular computing using conjugation for wiring.

Goñi-Moreno A, Amos M, de la Cruz F. PLoS One. 2013 Jun 20;8(6):e65986. doi: 10.1371/journal.pone.0065986.

[pubmed]

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CRISPR-Cas systems preferentially target the leading regions of MOBF conjugative plasmids.

Westra ER, Staals RH, Gort G, Høgh S, Neumann S, de la Cruz F, Fineran PC, Brouns SJ. RNA Biol. 2013 May;10(5):749-61. doi: 10.4161/rna.24202.

[pubmed]

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Evolution of Conjugation and Type IV Secretion Systems.

Guglielmini J, de la Cruz F, Rocha EP. Mol Biol Evol. 2013 Feb;30(2):315-31. doi: 10.1093/molbev/mss221.

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Ordering the bestiary of genetic elements transmissible by conjugation.

Garcillán-Barcia MP, de la Cruz F. Mob Genet Elements. 2013 Jan 1;3(1):e24263.

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The hexameric structure of a conjugative VirB4 protein ATPase provides new insights for a functional and phylogenetic relationship with DNA translocases.

Peña A, Martín-Benito J, Valpuesta JM, Carrascosa JL, de la Cruz F, Cabezón E*, Arechaga I*. J. Biol. Chem. 2012, 287(47), 39925-32. doi: 10.1074/jbc.M112.413849.

[pubmed]

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A degenerate primer MOB typing (DPMT) method to classify gamma-proteobacterial plasmids in clinical and environmental settings.

Alvarado A, Garcillán-Barcia MP, de la Cruz F. PLoS One. 2012;7(7):e40438.

[pubmed]

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Determination of conjugation rates on solid surfaces.

Del Campo I, Ruiz R, Cuevas A, Revilla C, Vielva L, de la Cruz F. Plasmid. 2012 Mar;67(2):174-82.

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Interaction between relaxase MbeA and accessory protein MbeC of the conjugally mobilizable plasmid ColE1.

Varsaki A, Lamb HK, Eleftheriadou O, Vandera E, Thompson P, Moncalián G, de la Cruz F, Hawkins AR, Drainas C. FEBS Lett. 2012 Mar 23;586(6):675-9.

[pubmed]

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Regulation of the type IV secretion ATPase TrwD by magnesium: implications for the catalytic mechanism of the secretion ATPase superfamily.

Ripoll-Rozada J, Peña A, Rivas S, Moro F, de la Cruz F, Cabezón E*,Arechaga I* J. Biol. Chem. 2012, 287(21), 17408-14. DOI:10.1074/jbc.M112.357905.

[pubmed]

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Autoinhibitory regulation of TrwK, an essential VirB4 ATPase in type IV secretion systems.

Peña A, Ripoll-Rozada J, Zunzunegui S, Cabezón E, de la Cruz F, Arechaga I* J. Biol. Chem. 2011, 286(19), 17376-82. DOI:10.1074/jbc.M110.208942.

​[pubmed]

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The conjugative DNA translocase TrwB is a structure specific DNA-binding protein.

Matilla I, Alfonso C, Rivas G, Bolt EL, de la Cruz F, Cabezón E* J. Biol. Chem. 2010, 285(23, 17537-44. DOI:10.1074/jbc.M109.084137.

​[pubmed]

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Relaxase DNA binding and cleavage are two distinguishable steps in conjugative DNA processing that involve different sequence elements of the nic site.

Lucas M, Gonzalez-Perez B, Cabezas M, Moncalián G, Rivas G, de la Cruz F. J Biol Chem. 2010 Mar 19; 285(12):8918-26. doi: 10.1074/jbc.M109.057539

[PubMed]

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Miguel Baez Martín

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Roger Bartomeus Peñalver

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Raúl Fernández López

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Ana González Guerra

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Sheila González Gutiérrez

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Raquel Gutiérrez Lanza

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Alfonso Mendaña Gomez

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Carolina Palencia Gándara

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Jorge Rodríguez Grande

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Irene Sanz Puente

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