Publications

2024

• The circularly permuted globin domain of Androglobin exhibits atypical heme stabilization and nitric oxide interaction
  
  • Reeder Brandon J
  • Deganutti Giuseppe
  • Ukeri John
  • Atanasio Silvia
  • Svistunenko Dimitri A
  • Ronchetti Christopher
  • Mobarec Juan Carlos
  • Welbourn Elizabeth
  • Asaju Jeffrey
  • Vos Marten H
  • Wilson Michael T
  • Reynolds Christopher A
  Chemical Science, The Royal Society of Chemistry, 2024, 15 (18), pp.6738-6751. In the decade since the discovery of androglobin, a multi-domain hemoglobin of metazoans associated with ciliogenesis and spermatogenesis, there has been little advance in the knowledge of the biochemical and structural properties of this unusual member of the hemoglobin superfamily. Using a method for aligning remote homologues, coupled with molecular modelling and molecular dynamics, we have identified a novel structural alignment to other hemoglobins. This has led to the first stable recombinant expression and characterization of the circularly permuted globin domain. Exceptional for eukaryotic globins is that a tyrosine takes the place of the highly conserved phenylalanine in the CD1 position, a critical point in stabilizing the heme. A disulfide bond, similar to that found in neuroglobin, forms a closed loop around the heme pocket, taking the place of androglobin’s missing CD loop and further supporting the heme pocket structure. Highly unusual in the globin superfamily is that the heme iron binds nitric oxide as a five-coordinate complex similar to other heme proteins that have nitric oxide storage functions. With rapid autoxidation and high nitrite reductase activity, the globin appears to be more tailored toward nitric oxide homeostasis or buffering. The use of our multi-template profile alignment method to yield the first biochemical characterisation of the circularly permuted globin domain of androglobin expands our knowledge of the fundamental functioning of this elusive protein and provides a pathway to better define the link between the biochemical traits of androglobin with proposed physiological functions. (10.1039/D4SC00953C)
  DOI : 10.1039/D4SC00953C
• Mesure de la transparence cornéenne par l’analyse d’images oct
  
  • Plamann Karsten
  • Vilbert Maëlle
  • Bocheux Romain
  • Georgeon Cristina
  • Borderie Vincent
  • Pernot Pascal
  • Irsch Kristina
  Photoniques, EDP Sciences, 2024 (127), pp.46-51. La cornée est la première des deux lentilles de l’oeil. La transparence de la cornée saine est due à sa structure très régulière qui peut être perturbée en présence de pathologies. Pour diagnostiquer la transparence cornéenne, nous avons développé des méthodes basées sur l’analyse d’images obtenues par tomographie par cohérence optique (OCT) qui permettent d’obtenir des valeurs physiques comme le libre parcours moyen des photons et le pourcentage de transmission cohérente de la lumière, qui impactent la vision. (10.1051/photon/202412746)
  DOI : 10.1051/photon/202412746
• Structure of a DNA G-quadruplex that Modulates SP1 Binding Sites Architecture in HIV-1 Promoter
  
  • de Rache Aurore
  • Marquevielle Julien
  • Bouaziz Serge
  • Vialet Brune
  • Andreola Marie-Line
  • Mergny Jean-Louis
  • Amrane Samir
  Journal of Molecular Biology, Elsevier, 2024, 436 (2), pp.168359. Nucleic acid sequences containing guanine tracts are able to form non-canonical DNA or RNA structures known as G-quadruplexes (or G4s). These structures, based on the stacking of G-tetrads, are involved in various biological processes such as gene expression regulation. Here, we investigated a G4 forming sequence, HIVpro2, derived from the HIV-1 promoter. This motif is located 60 nucleotides upstream of the proviral Transcription Starting Site (TSS) and overlaps with two SP1 transcription factor binding sites. Using NMR spectroscopy, we determined that HIVpro2 forms a hybrid type G4 structure with a core that is interrupted by a single nucleotide bulge. An additional reverse-Hoogsteen AT base pair is stacked on top of the tetrad. SP1 transcription factor is known to regulate transcription activity of many genes through the recognition of Guanine-rich duplex motifs. Here, the formation of HIVpro2 G4 may modulate SP1 binding sites architecture by competing with the formation of the canonical duplex structure. Such DNA structural switch potentially participates to the regulation of viral transcription and may also interfere with HIV-1 reac- tivation or viral latency. (10.1016/j.jmb.2023.168359)
  DOI : 10.1016/j.jmb.2023.168359
• The control of nitric oxide dynamics and interaction with substituted zinc-phthalocyanines
  
  • Ben Brahim Nassim
  • Touaiti Sarra
  • Sellés Julien
  • Lambry Jean-Christophe
  • Negrerie Michel
  Dalton Transactions, Royal Society of Chemistry, 2024, 53 (2), pp.772-780. Phthalocyanines are artificial macrocycles that can harbour a central metal atom with four symmetric coordinations. Similar to metal-porphyrins, metal-phthalocyanines (M-PCs) may bind small molecules, especially diatomic gases such as NO and O2. Furthermore, various chemical chains can be grafted at the periphery of the M-PC macrocycle, which can change its properties, including the interaction with diatomic gases. In this study, we synthesized Zn-PCs with two different substituents and investigated their effects on the interaction and dynamics of nitric oxide (NO). Time-resolved absorption spectroscopy from picosecond to millisecond revealed that NO dynamics dramatically depends on the nature of the groups grafted to the Zn-PC macrocycle. These experimental results were rationalized by DFT calculations, which demonstrate that electrostatic interactions between NO and the quinoleinoxy substituent modify the potential energy surface and decrease the energy barrier for NO recombination, thus controlling its affinity. (10.1039/d3dt03356b)
  DOI : 10.1039/d3dt03356b