Structural biology of protein & nucleic acid complexes and molecular machines
Miquel Coll
Group Leader
Professor (IBMB-CSIC)
Office Tel : +34 93 40 34951
e-mail : miquel.coll
irbbarcelona.org
Background
Our research focuses on the three-dimensional structure of proteins, nucleic acids and their complexes with the aim to further our understanding of several essential mechanisms in the cell. We use a number of molecular biology and structural biology techniques, with a focus on X-ray diffraction crystallography. Our approach usually starts with the cloning of relevant genes and the expression and purification of the encoded proteins. Proteins, nucleic acids and their complexes are then crystallized and analysed by X-ray diffraction, using synchrotron radiation. The final outcome is a detailed 3D view of the molecular structures at atomic resolution.
Research Interests
We examine systems related to horizontal gene transfer which involve the DNA translocation across the cell membranes. In addition, we address the regulatory mechanisms of gene expression and the control mechanisms of DNA replication. We also study unique DNA structures, like DNA junctions, and novel drugs that target DNA.
Research Lines
DNA replication control. Plasmids are extra-chromosomal DNA molecules that replicate autonomously. In pathogenic bacteria, plasmids may carry antibiotic resistance genes. Plasmid replication is controlled by gene products encoded in the plasmid itself. In collaboration with Manuel Espinosa and Gloria del Solar (CIB-CSIC), we are currently studying this system in streptococcal plasmids.
Horizontal gene transfer. Conjugation is the main route for horizontal gene transfer in bacteria and is responsible for the spread of antibiotic resistance. During conjugation, plasmid DNA is processed and transported across cell membranes between cells. The relaxosome is a protein-DNA complex formed by several proteins and a DNA segment called the Origin of Transfer. The transport complex is a transmembrane multiprotein assembly. In collaboration with Fernando de la Cruz (U. of Cantabria), we are examining this system in E. coli plasmid R388.
DNA packaging in viruses. Portal proteins or connectors are large multimeric proteins involved in DNA packaging into viral capsids. With the help of other proteins, they translocate the DNA through one vertex of the capsid. We are currently analysing various connectors and other related DNA packaging proteins, in collaboration with José L. Carrsacosa and José María Valpuesta (CNB-CSIC).
Transcription regulation. We study several transcription factors and their complexes with other proteins and DNA promoter regions. In collaboration with Margarita Salas (CBM-CSIC), in bacteriophage φ29 we examine the transcriptional regulator p4 that functions as a switch between early and late gene expression during the infection cycle. In E.coli, we address the PhoB transcriptional activator, a response regulator of the two-component signal transduction system that controls the expression of more than 40 genes related to phosphate assimilation.
DNA structure and drug-DNA interactions. Unique DNA structures, such as four-way and three-way junctions related to DNA recombination and other processes, are being structurally analysed. Novel DNA-binding drugs that target these peculiar structures and other sequence-specific drugs are also under study.
Viral replication machinery. Within the Structural Genomics European Consortium VIZIER, the replication enzymes and ancillary proteins of human pathogenic RNA virus are currently being structurally characterized. The final aim is to provide tools for the discovery of new antiviral agents.
Protein complexes, epigenetic regulation of gene expression and cancer. As a partner of the European Consortium 3D-REPERTOIRE and coordinator of the Spanish Structural Genomics Consortium GENES, our group studies several protein complexes and molecular machines, some of which are related to the epigenetic control of gene expression. Targets for anticancer therapy are among the proteins currently being analysed.
Funding
This group receives financial support from the following sources:
- European Union
- Ministerio de Educación y Ciencia (Spanish Ministry of Science & Education)
- Ministerio de Industria, Turismo y Comercio (Spanish Ministry of Industry, Tourism and Trade)
- Generalitat de Catalunya (Government of Catalonia)
- Fundació La Marató de TV3 ("La Marató TV3" Foundation)
More info
Structural biology of protein & nucleic acid complexes and molecular machines
Molecular architecture of the Mn2+-dependent lactonase UlaG reveals an RNase-like metallo-beta-lactamase fold and a novel quaternary structure
Garces F, Fernández FJ, Montellŕ C, Penya-Soler E, Prohens R, Aguilar J, Baldomŕ L, Coll M, Badia J and Vega MC
J Mol Biol, 398 (5), 715-729 (2010)
Self-assembly of functionalizable two-component 3D DNA arrays through the induced formation of DNA three-way-junction branch points by supramolecular cylinders
Boer DR, Kerckhoffs JM, Parajo Y, Pascu M, Usón I, Lincoln P, Hannon MJ and Coll M
Angew Chem Int Ed Engl, 49 (13), 2336-2339 (2010)
Human mitochondrial mTERF wraps around DNA through a left-handed superhelical tandem repeat
Jiménez-Menéndez N, Fernández-Millán P, Rubio-Cosials A, Arnan C, Montoya J, Jacobs HT, Bernadó P, Coll M, Usón I and Solŕ M
Nat Struct Mol Biol, 17 (7), 891-893 (2010)
The structure of RNA-free Rho termination factor indicates a dynamic mechanism of transcript capture
Canals A, Usón I and Coll M
J Mol Biol, 400 (1), 16-23 (2010)
Structure and inhibition of herpesvirus DNA packaging terminase nuclease domain
Nadal M, Mas PJ, Blanco AG, Arnan C, Solŕ M, Hart DJ, Coll M.
Proc Natl Acad Sci U S A, 107 (37), 16078-16083 (2010)
Cloning, expression, purification and crystallization of the Rho transcription termination factor from Thermotoga maritima
Canals A and Coll M
Protein Expr Purif, 65 (2), 174-178 (2009)
DNA-binding drugs caught in action: the latest 3D pictures of drug-DNA complexes
Boer DR, Canals A and Coll M
Dalton Trans, 3, 399-414 (2009)
Plasmid replication initiator RepB forms a hexamer reminiscent of ring helicases and has mobile nuclease domains
Boer DR, Ruíz-Masó JA, López-Blanco JR, Blanco AG, Vives-Llŕcer M, Chacón P, Usón I, Gomis-Rüth FX, Espinosa M, Llorca O, Del Solar G and Coll M
EMBO J, 28 (11), 1666-1678 (2009)
DNA-binding drugs caught in action: the latest 3D pictures of drug-DNA complexes
Boer DR, Canals A and Coll M
Dalton Trans, 3 (399), 414 (2009)
Molecular Machinery for DNA Translocation in Bacterial Conjugation
Russi S, Boer R and Coll M
Plasmids: Current Research and Future Trends. Horizon Scientific Press, London. ISBN: 978-1-904455-35-6 (2008)
Quaternary structural transitions in the DeoR-type repressor UlaR control transcriptional readout from the L-ascorbate utilization regulon in Escherichia coli
Garces F, Fernández FJ, Gómez AM, Pérez-Luque R, Campos E, Prohens R, Aguilar J, Baldomŕ L, Coll M, Badía J and Vega MC
Biochemistry, 47 (44), 11424-11433 (2008)
The VIZIER project: preparedness against pathogenic RNA viruses
Coutard B, Gorbalenya AE, Snijder EJ, Leontovich AM, Poupon A, De Lamballerie X, Charrel R, Gould EA, Gunther S, Norder H, Klempa B, Bourhy H, Rohayem J, L'hermite E, Nordlund P, Stuart DI, Owens RJ, Grimes JM, Tucker PA, Bolognesi M, Mattevi A, Coll M, Jones TA, Aqvist J, Unge T, Hilgenfeld R, Bricogne G, Neyts J, La Colla P, Puerstinger G, Gonzalez JP, Leroy E, Cambillau C, Romette JL and Canard B
Antiviral Res, 78 (1), 37-46 (2008)
Quaternary structural transitions in the DeoR-type repressor UlaR control transcriptional readout from the L-ascorbate utilization regulon in Escherichia coli
Garces F, Fernández FJ, Gómez AM, Pérez-Luque R, Campos E, Prohens R, Aguilar J, Baldomŕ L, Coll M, Badía J and Vega MC
Biochemistry, 44 (11424), 11433 (2008)
Overproduction, crystallization and preliminary X-ray analysis of the putative L-ascorbate-6-phosphate lactonase UlaG from Escherichia coli
Garces F, Fernández FJ, Pérez-Luque R, Aguilar J, Baldomŕ L, Coll M, Badía J and Vega MC
Acta Crystallogr Sect F Struct Biol Cryst Commun, 64 (Pt1), 36-38 (2008)
The VIZIER project: Preparedness against pathogenic RNA viruses
Coutard B, Gorbalenya AE, Snijder EJ, Leontovich AM, Poupon A, De Lamballerie X, Charrel R, Gould EA, Gunther S, Norder H, Klempa B, Bourhy H, Rohayem J, L'hermite E, Nordlund P, Stuart DI, Owens RJ, Grimes JM, Tucker PA, Bolognesi M, Mattevi A, Coll M, Jones TA, Aqvist J, Unge T, Hilgenfeld R, Bricogne G, Neyts J, La Colla P, Puerstinger G, Gonzalez JP, Leroy E, Cambillau C, Romette JL, Canard B.
Antiviral Res (2007)
Overproduction, crystallization and preliminary X-ray analysis of the putative L-ascorbate-6-phosphate lactonase UlaG from Escherichia coli
Garces F, Fernández FJ, Pérez-Luque R, Aguilar J, Baldomŕ L, Coll M, Badía J, Vega MC
Acta Crystallogr Sect F Struct Biol Cryst Commun (2007)
The cofactor-induced pre-active conformation in PhoB.
Solŕ M, Drew DL, Blanco AG, Gomis-Rüth FX, Coll M.
Acta Crystallogr D Biol Crystallogr, 62 (Pt 9), 1046-1057 (2006)
The structure of phage φ29 transcription regulator p4-DNA complex reveals an N-hook motif for DNA binding
Badia D, Camacho A, Pérez-Lago L, Escandón C, Salas M &Coll M
Molecular Cell, 22, 73-81 (2006)
Molecular recognition of a three-way DNA junction by a metallo-supramolecular helicate
Oleksi A, Blanco AG, Boer R, Usón I, Aymamí J, Rodger A, Hannon MJ & Coll M
Angewandte ChemieInt., 45, 1227-1231 (2006)
Unveiling the molecular mechanism of a conjugative relaxase: The structure of TrwC complexed with a 27-mer DNA comprising the recognition hairpin and the cleavage site
Boer R, Russi S, Guasch A, Lucas M, Blanco AG, Pérez-Luque R, Coll M and De la Cruz F
J Mol Biol., 358, 857-869 (2006)
Application of the use of high-throughput technologies to the determination of protein structures of bacterial and viral pathogens
Fogg MJ, Alzari P, Bahar M, Bertini I, Betton JM, Burmeister WP, Cambillau C, Canard B, Carrondo M, Coll M, Daenke S, Dym O, Egloff MP, Enguita FJ, Geerlof A, Haouz A, Jones TA, Ma Q, Manicka SN, Migliardi M, Nordlund P, Owens RJ, Peleg Y, Schneider G, Schnell R, Stuart DI, Tarbouriech N, Unge T, Wilkinson AJ, Wilmanns M, Wilson KS, Zimhony O, and Grimes JM
Acta Crustallogr D Biol Crystallogr, 62, 1196-1207 (2006)
The X-ray crystal structures of two constitutively active mutants of the E. coli PhoB receiver domain give insights into activation
Arribas-Bosacoma R, Kim S-K, Ferrer-Orta C, Blanco AG, Pereira P JB, Gomis-Rüth X, Wanner BL, Coll M and Solŕ M
J Mol Biol., 366, 626-641 (2006)
Cut and Move: Protein Machinery for DNA Processing in Bacterial Conjugation
Gomis-Rüth FX and Coll M
Curr Opin Struct Biol, 16, 744-752 (2006)
Crystal structure of an iron-dependent group III dehydrogenase that interconverts L-lactaldehyde and L-1,2-propanediol in Escherichia coli
Montella C, Bellsolell L, Pérez-Luque R, Badía J, Baldoma L, Coll M, Aguilar J.
J Bacteriol., 187 (14), 4957-4966 (2005)
The anticancer agent ellipticine unwinds DNA by intercalative binding in an orientation parallel to base pairs.
Canals A, Purciolas M, Aymamí J, Coll M.
Acta Crystallogr D Biol Crystallogr., 61 (Pt 7), 1009-1012 (2005)
Recognition and processing of the origin of transfer DNA by conjugative relaxase TrwC
Guasch A, Lucas M, Moncalián G, Cabezas M, Pérez-Luque R,Gomis-Rüth FX, de la Cruz F & Coll M
Nature Structural and Molecular Biology, 10, 1002-1010 (2003)
Structure of the DNA-bound T-box domain of human TBX3, a transcription factor responsible for ulnar-mammary syndrome.
Coll M, Seidman JG, Müller CW.
Structure, 10 (3), 343-356 (2002)
Conjugative plasmid protein TrwB, an integral membrane type IV secretion system coupling protein. Detailed structural features and mapping of the active site cleft
Gomis-Rüth FX, Moncalían G, de la Cruz F, Coll M.
J Biol Chem., 277 (9), 7556-7566 (2002)
Detailed architecture of a DNA translocating machine: the high-resolution structure of the bacteriophage phi29 connector particle.
Guasch A, Pous J, Ibarra B, Gomis-Rüth FX, Valpuesta JM, Sousa N, Carrascosa JL, Coll M.
J Mol Biol., 315 (4), 663-676 (2002)
Crystallization and preliminary X-ray analysis of the DNA decamers d(CCGGATCCGG) and d(CCGGCGCCGG)
Aymami J, Pous J, Lisgarten JN, Coll M.
Acta Crystallogr D Biol Crystallogr., 58 (Pt 2), 310-311 (2002)
Crystallization and preliminary X-ray analysis of the antimalarial and cytotoxic alkaloid cryptolepine complexed with the DNA fragment d(CCTAGG)2.
Lisgarten JN, Pous J, Coll M, Wright CW, Aymami J.
Acta Crystallogr D Biol Crystallogr., 58 (Pt 2), 312-313 (2002)
Tandem DNA recognition by PhoB, a two-component signal transduction transcriptional activator
Blanco AG, Sola M, Gomis-Rüth FX & Coll M
Structure, 10, 1-20 (2002)
Trypanosoma cruzi macrophage infectivity potentiator has arotamase core and a highly exposed α-helix
Pereira PJB, Vega MC, González-Rey E, Fernández-Carazo R, Macedo-Ribeiro S, Gomis-Rüth FX, González A & Coll M
EMBO reports, 3, 88-94 (2002)
The antimalarial and cytotoxic drug cryptolepineintercalates into DNA at cytosine-cytosine sites
Lisgarten JN, Coll M, Portugal J, Wright CW & Aymamí J
Nature Structural Biology, , 9, 57-60 (2002)
Structure of TrwB, a gatekeeper in bacterial conjugation.
Gomis-Rüth FX, Coll M.
Int J Biochem Cell Biol., 33 (9), 839-843 (2001)
The structure of an engineered domain-swapped ribonuclease dimer and its implications for the evolution of proteins toward oligomerization.
Canals A, Pous J, Guasch A, Benito A, Ribó M, Vilanova M, Coll M.
Structure, 9 (10), 967-976 (2001)
The crystal structure of the inhibitor-complexed carboxypeptidase D domain II and the modeling of regulatory carboxypeptidases.
Aloy P, Companys V, Vendrell J, Aviles FX, Fricker LD, Coll M, Gomis-Rüth FX.
J Biol Chem., 276 (19), 16177-16184 (2001)
Three-dimensional structure of human biliverdin-IXβ reductase, an early fetal bilirubin-IXβ producing enzyme
Pereira PJ, Macedo-Ribeiro S, Párraga A, Pérez-Luque R, Cunningham O, Darcy K, Mantle TJ, Coll M.
Nat Struct Biol, 8 (3), 215-220 (2001)
Solving a 300-kDa multimeric protein by low-resolution MAD phasing and averaging/phase extension.
Gomis-Rüth FX, Coll M.
Acta Crystallogr D Biol Crystallogr., 57 (Pt 6), 489-505 (2001)
Plasmid transcriptional repressor CopG oligomerises to render helical superstructures unbound and in complexes with oligonucleotides.
Costa M, Solŕ M, del Solar G, Eritja R, Hernández-Arriaga AM, Espinosa M, Gomis-Rüth FX, Coll M.
J Mol Biol., 310 (2), 403-417 (2001)
Review: postchaperonin tubulin folding cofactors and their role in microtubule dynamics
Lopez-Fanarraga M, Avila J, Guasch A, Coll M, Zabala JC.
J Struct Biol., 135 (2), 219-229 (2001)
Three-dimensional structure of human RNase 1 delta N7 at 1.9 A resolution.
Pous J, Mallorquí-Fernández G, Peracaula R, Terzyan SS, Futami J, Tada H, Yamada H, Seno M, de Llorens R, Gomis-Rüth FX, Coll M.
Acta Crystallogr D Biol Crystallogr, 57 (Pt 4), 498-505 (2001)
Structure of human biliverdin-IXβ reductase, an earlyfetal bilirubin-IXβ producing enzyme
Pereira PJ, Macedo-Ribeiro S, Párraga A, Pérez-Luque R, Cunningham O, Darcy K, Mantle TJ and Coll M
Nat Struct Biol, 8 (3), 215-220 (2001)
The bacterial conjugation protein TrwB resembles ring helicases and F1-ATPase
Gomis-Rüth FX, Moncalián G, Pérez-Luque R, González A, Cabezón E, de la Cruz F and Coll M
Nature, 409, 637-641 (2001)
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