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Miquel Coll

Publications and source records attributed to Miquel Coll.

25 records · Page 2Linked to original sources
PubMed2002

Structure of the DNA-bound T-box domain of human TBX3, a transcription factor responsible for ulnar-mammary syndrome.

T-box genes encode transcription factors involved in morphogenesis and organogenesis of vertebrates and invertebrates. Mutations in human T-box genes TBX3, TBX5, and TBX1 cause severe genetic disorders known as Ulnar-Mammary syndrome (UMS), Holt-Oram syndrome (HOS), and DiGeorge syndrome, respectively. The crystal structure of the T-box domain of the first human T-box transcription factor, TBX3, in complex with DNA at 1.7 A resolution explains structural consequences of T-box domain point mutations observed in UMS and HOS patients. Comparison with the structure of the T-box domain from Xenopus laevis (Xbra) bound to DNA shows differences in several secondary structure elements and in the quaternary structure of the two complexes. TBX3 independently recognizes the two binding sites present in the palindromic DNA duplex, whereas in Xbra, binding to the palindrome is stabilized through interactions between the two monomers. The different quaternary structures suggest different DNA binding modes for T-box transcription factors.

Abnormalities, Multiple↗
PubMed2002

Tandem DNA recognition by PhoB, a two-component signal transduction transcriptional activator.

PhoB is a signal transduction response regulator that activates nearly 40 genes in phosphate depletion conditions in E. coli and closely related bacteria. The structure of the PhoB effector domain in complex with its target DNA sequence, or pho box, reveals a novel tandem arrangement in which several monomers bind head to tail to successive 11-base pair direct-repeat sequences, coating one face of a smoothly bent double helix. The protein has a winged helix fold in which the DNA recognition elements comprise helix alpha 3, penetrating the major groove, and a beta hairpin wing interacting with a compressed minor groove via Arg219, tightly sandwiched between the DNA sugar backbones. The transactivation loops protrude laterally in an appropriate orientation to interact with the RNA polymerase sigma(70) subunit, which triggers transcription initiation.

Amino Acid Sequence↗
PubMed2002

The antimalarial and cytotoxic drug cryptolepine intercalates into DNA at cytosine-cytosine sites.

Cryptolepine, a naturally occurring indoloquinoline alkaloid used as an antimalarial drug in Central and Western Africa, has been found to bind to DNA in a formerly unknown intercalation mode. Evidence from competition dialysis assays demonstrates that cryptolepine is able to bind CG-rich sequences containing nonalternating CC sites. Here we show that cryptolepine interacts with the CC sites of the DNA fragment d(CCTAGG)(2) in a base-stacking intercalation mode. This is the first DNA intercalator complex, from approximately 90 solved by X-ray crystallography, to bind a nonalternating (pyrimidine-pyrimidine) DNA sequence. The asymmetry of the drug induces a perfect stacking with the asymmetric site, allowing for the stability of the complex in the absence of hydrogen bonding interactions. The crystal structure of this antimalarial drug-DNA complex provides evidence for the first nonalternating intercalation and, as such, provides a basis for the design of new anticancer or antimalarial drugs.

Alkaloids↗
PubMed2002

Bacterial conjugation: a two-step mechanism for DNA transport.

Bacterial conjugation is a promiscuous DNA transport mechanism. Conjugative plasmids transfer themselves between most bacteria, thus being one of the main causal agents of the spread of antibiotic resistance among pathogenic bacteria. Moreover, DNA can be transferred conjugatively into eukaryotic host cells. In this review, we aim to address several basic questions regarding the DNA transfer mechanism. Conjugation can be visualized as a DNA rolling-circle replication (RCR) system linked to a type IV secretion system (T4SS), the latter being macromolecular transporters widely involved in pathogenic mechanisms. The scheme 'replication + secretion' suggests how the mechanism would work on the DNA substrate and at the bacterial membrane. But, how do these two parts come into contact? Furthermore, how is the DNA transported? T4SS are known to be involved in protein secretion in different organisms, but DNA is a very different macromolecule. The so-called coupling proteins could be the answer to both questions by performing a dual role in conjugation: coupling the two main components of the machinery (RCR and T4SS) and actively mediating DNA transport. We postulate that the T4SS is responsible for transport of the pilot protein (the relaxase) to the recipient. The DNA that is covalently linked to it is initially transported in a passive manner, trailing on the relaxase. We speculate that the pilus appendage could work as a needle, thrusting the substrate proteins to cross one or several membrane barriers into the recipient cytoplasm. This is the first step in conjugation. The second step is the active pumping of the DNA to the recipient, using the already available T4SS transport conduit. It is proposed that this second step is catalysed by the coupling proteins. Our 'shoot and pump' model solves the protein-DNA transport paradox of T4SS.

Bacteria↗
PubMed2001

Trypanosoma cruzi macrophage infectivity potentiator has a rotamase core and a highly exposed alpha-helix.

The macrophage infectivity potentiator protein from Trypanosoma cruzi (TcMIP) is a major virulence factor secreted by the etiological agent of Chagas' disease. It is functionally involved in host cell invasion. We have determined the three-dimensional crystal structure of TcMIP at 1.7 A resolution. The monomeric protein displays a peptidyl-prolyl cis-trans isomerase (PPIase) core, encompassing the characteristic rotamase hydrophobic active site, thus explaining the strong inhibition of TcMIP by the immunosuppressant FK506 and related drugs. In TcMIP, the twisted beta-sheet of the core is extended by an extra beta-strand, preceded by a long, exposed N-terminal alpha-helix, which might be a target recognition element. An invasion assay shows that the MIP protein from Legionella pneumophila (LpMIP), which has an equivalent N-terminal alpha-helix, can substitute for TcMIP. An additional exposed alpha-helix, this one unique to TcMIP, is located in the C-terminus of the protein. The high-resolution structure reported here opens the possibility for the design of new inhibitory drugs that might be useful for the clinical treatment of American trypanosomiasis.

Amino Acid Sequence↗
PubMed2001

Conjugative plasmid protein TrwB, an integral membrane type IV secretion system coupling protein. Detailed structural features and mapping of the active site cleft.

Bacterial conjugation is an example of macromolecular trafficking between cells and responsible for the spreading of antibiotic resistance among bacteria. It involves translocation of single-stranded DNA across membranes through a type IV secretion system. A coupling protein links the DNA-processing nucleoprotein complex, the relaxosome, with the transport apparatus during cell mating. In Escherichia coli plasmid R388 such a protein is TrwB, a basic integral inner-membrane nucleoside-triphosphate-binding protein. TrwB is the structural prototype for the type IV secretion system coupling proteins, a family of proteins essential for macromolecular transport between cells and export. The structure of a soluble TrwB variant unveils an elongated molecule with six equivalent protein units featuring a spherical quaternary structure, leaving a central channel. The structures of the non-liganded protein and four different complexes with substrate analogues and products allow the precise description of the active site architecture. The active sites are located at the interface between protomers, each of them shaped mainly by residues of one monomer, but including two crucial arginine residues belonging to the adjacent molecule. Upon substrate binding and putative hydrolysis, conformational changes are transferred from the external surface to the interior central channel.

Anions↗