David Vizarraga Revuelto

@csic.es

PhD student, Crystallography Department/ CSIC
Institute of Molecular Biology of Barcelona (IBMB)

David Vizarraga Revuelto


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https://researchid.co/davidviza
10

Scopus Publications

201

Scholar Citations

5

Scholar h-index

4

Scholar i10-index

Scopus Publications

  • In silico design of stable single-domain antibodies with high affinity
    Zhongyao Zhang, Rob van der Kant, Iva Marković, David Vizarraga, Teresa Garcia, Katerina Maragkou, Javier Delgado Blanco, Damiano Cianferoni, Gabriele Orlando, Gabriel Cia, Nick Geukens, Carlo Carolis, Alexander N. Volkov, Savvas N. Savvides, Maarten Dewilde, Joost Schymkowitz, Luis Serrano Pubul, Frederic Rousseau
    Structure, 2026
  • Sources of essential lipids for Mycoplasma pneumoniae via P116 to target liver and atherosclerotic lesions
    David Vizarraga, Marina Marcos, Noemi Rotllan, Jesús Martín, David Santos, Mercedes Camacho, Begoña Soto, Lorena Velasco-Reniu, Pablo Guerra, Félix Pareja, María Collantes, Wanlu Wu, Irene Rodríguez-Arce, Luis Serrano, Jaume Piñol, Ignacio Fita, Joan Carles Escolà-Gil
    Nature Communications, 2025
    Mycoplasma pneumoniae (MPN) is a bacterial pathogen that primarily causes atypical pneumonia. It cannot synthesize certain essential lipids and therefore relies on the host for their acquisition to survive. MPN has been detected in increased amounts within ruptured atherosclerotic plaques. In this work, we show that the protein P116 facilitates cholesterol acquisition from LDL, HDL and various cell types. Targeting P116’s C-terminal domain with a monoclonal antibody inhibits cholesterol acquisition and bacterial growth in vitro. Phase contrast epifluorescence microscopy of human arteries reveals that this antibody blocks MPN binding to atherosclerotic lesions ex vivo. Additionally, an MPN chassis injected into hyperlipidemic female mice localizes to the liver and atherosclerotic plaques. Here, we report that P116 plays a role in extracting essential lipids from lipoproteins and host cells and regulates MPN localization to atheromatous plaques. The study highlights MPN’s potential as a tool for targeting atherosclerotic lesions and fatty liver. In this work, the authors show that the essential Mycoplasma pneumoniae protein P116 enables cholesterol acquisition from lipoproteins and various cell types. An antibody against its C-terminal domain inhibits lipid acquisition, growth, and plaque binding, linking M. pneumoniae to atherosclerotic lipid-rich tissue.
  • Artificial intelligence and first-principle methods in protein redesign: A marriage of convenience?
    Damiano Cianferoni, David Vizarraga, Ana María Fernández‐Escamilla, Ignacio Fita, Rahma Hamdani, Raul Reche, Javier Delgado, Luis Serrano
    Protein Science, 2025
    Since AlphaFold2's rise, many deep learning methods for protein design have emerged. Here, we validate widely used and recognized tools, compare them with first‐principle methods, and explore their combinations, focusing on their effectiveness in protein redesign and potential for therapeutic repurposing. We address two challenges: evaluating tools and combinations ability to detect the effects of multiple concurrent mutations in protein variants, and leveraging large‐scale datasets to compare modeling‐free methods, namely force fields, which handle point mutations well with limited backbone rearrangement, and inverse folding tools, which excel at native sequence recovery but may struggle with non‐natural proteins. Debuting TriCombine, a tool that identifies residue triangles in input structures, matches them to a structural database, and scores mutants based on substitution frequencies, we shortlisted candidates, modeled them with FoldX, and generated 16 SH3 mutants carrying up to 9 concurrent substitutions. The dataset was expanded to include 36 mutants and 11 crystal structures (7 newly solved), along with a parallel set of multiple non‐concurrent mutants from three additional proteins. For broader validation, we analyzed 160,000 four‐site GB1 mutants and 163,555 (single and double) variants across 179 natural and de novo domains. We show that combining AI‐based modeling tools with force field scoring functions yields the most reliable results. Inverse folding tools perform very well but lose accuracy on less‐represented proteins. First‐principle force fields like FoldX remain the most accurate for point mutations. All methods perform worse when applied to unsolved de novo models, underscoring the need for hybrid strategies in robust protein design.
  • Dynamics of the adhesion complex of the human pathogens Mycoplasma pneumoniae and Mycoplasma genitalium
    David Vizarraga, Akihiro Kawamoto, Marina Marcos-Silva, Jesús Martín, Fumiaki Makino, Tomoko Miyata, Jorge Roel-Touris, Enrique Marcos, Oscar Q. Pich, David Aparicio, Ignacio Fita, Makoto Miyata, Jaume Piñol, Keiichi Namba, Tsuyoshi Kenri
    Plos Pathogens, 2025
    Mycoplasma pneumoniae and Mycoplasma genitalium are bacterial wall-less human pathogens and the causative agents of respiratory and reproductive tract infections. Infectivity, gliding motility and adhesion of these mycoplasmas to host cells are mediated by orthologous adhesin proteins forming a transmembrane adhesion complex that binds to sialylated oligosaccharides human cell ligands. Here we report the cryo-EM structure of M. pneumoniae P1 adhesin bound to the Fab fragment of monoclonal antibody P1/MCA4, which stops gliding and induces detachment of motile cells. The epitope of P1/MCA4 involves residues only from the small C-domain of P1. This epitope is accessible to antibodies only in the “closed conformation” of the adhesion complex and is not accessible in the “open” conformation, when the adhesion complex is ready for attachment to sialylated oligosaccharides. Polyclonal antibodies generated against the large N-domain of P1 or against the whole ectodomain of P40/P90 have little or no effects on adhesion or motility. Moreover, mutations in the highly conserved Engelman motifs found in the transmembrane helix of M. genitalium P110 adhesin also alter adhesion and motility. These results show that antibodies directed to the C-domain of P1 hinder the large conformational rearrangements in this domain required to alternate between the “open” and “closed” conformations of the adhesion complex. Since transition between both conformations is essential to complete the attachment/detachment cycle of the adhesion complex, interfering with the gliding of mycoplasma cells and providing a new potential target to confront M. pneumoniae and M. genitalium infections.
  • Molecular basis of bacterial lectin recognition of eukaryotic glycans: The case of Mycoplasma pneumoniae and Mycoplasma genitalium cytoadhesins
    Angela Marseglia, Maria Concetta Forgione, Marina Marcos-Silva, Cristina Di Carluccio, Yoshiyuki Manabe, David Vizarraga, Ferran Nieto-Fabregat, Maria Pia Lenza, Koichi Fukase, Antonio Molinaro, Oscar Q. Pich, David Aparicio, Alba Silipo, Roberta Marchetti
    International Journal of Biological Macromolecules, 2024
  • Essential protein P116 extracts cholesterol and other indispensable lipids for Mycoplasmas
    Lasse Sprankel, David Vizarraga, Jesús Martín, Sina Manger, Jakob Meier-Credo, Marina Marcos, Josep Julve, Noemi Rotllan, Margot P. Scheffer, Joan Carles Escolà-Gil, Julian D. Langer, Jaume Piñol, Ignacio Fita, Achilleas S. Frangakis
    Nature Structural and Molecular Biology, 2023
    Mycoplasma pneumoniae, responsible for approximately 30% of community-acquired human pneumonia, needs to extract lipids from the host environment for survival and proliferation. Here, we report a comprehensive structural and functional analysis of the previously uncharacterized protein P116 (MPN_213). Single-particle cryo-electron microscopy of P116 reveals a homodimer presenting a previously unseen fold, forming a huge hydrophobic cavity, which is fully accessible to solvent. Lipidomics analysis shows that P116 specifically extracts lipids such as phosphatidylcholine, sphingomyelin and cholesterol. Structures of different conformational states reveal the mechanism by which lipids are extracted. This finding immediately suggests a way to control Mycoplasma infection by interfering with lipid uptake.
  • The Sialoglycan Binding Adhesins of Mycoplasma genitalium and Mycoplasma pneumoniae
    David Vizarraga, Sergi Torres-Puig, David Aparicio, Oscar Q. Pich
    Trends in Microbiology, 2021
    Mycoplasma genitalium (Mge) and Mycoplasma pneumoniae (Mpn) are two human pathogens associated with urogenital and respiratory tract infections, respectively. The recent elucidation of the tridimensional structure of their major cytoadhesins by X-ray crystallography and cryo-electron microscopy/tomography, has provided important insights regarding the mechanics of infection and evasion of immune surveillance.
  • Structure and mechanism of the Nap adhesion complex from the human pathogen Mycoplasma genitalium
    David Aparicio, Margot P. Scheffer, Marina Marcos-Silva, David Vizarraga, Lasse Sprankel, Mercè Ratera, Miriam S. Weber, Anja Seybert, Sergi Torres-Puig, Luis Gonzalez-Gonzalez, Julian Reitz, Enrique Querol, Jaume Piñol, Oscar Q. Pich, Ignacio Fita, Achilleas S. Frangakis
    Nature Communications, 2020
    Mycoplasma genitalium is a human pathogen adhering to host target epithelial cells and causing urethritis, cervicitis and pelvic inflammatory disease. Essential for infectivity is a transmembrane adhesion complex called Nap comprising proteins P110 and P140. Here we report the crystal structure of P140 both alone and in complex with the N-terminal domain of P110. By cryo-electron microscopy (cryo-EM) and tomography (cryo-ET) we find closed and open Nap conformations, determined at 9.8 and 15 Å, respectively. Both crystal structures and the cryo-EM structure are found in a closed conformation, where the sialic acid binding site in P110 is occluded. By contrast, the cryo-ET structure shows an open conformation, where the binding site is accessible. Structural information, in combination with functional studies, suggests a mechanism for attachment and release of M. genitalium to and from the host cell receptor, in which Nap conformations alternate to sustain motility and guarantee infectivity.
  • Immunodominant proteins P1 and P40/P90 from human pathogen Mycoplasma pneumoniae
    David Vizarraga, Akihiro Kawamoto, U. Matsumoto, Ramiro Illanes, Rosa Pérez-Luque, Jesús Martín, Rocco Mazzolini, Paula Bierge, Oscar Q. Pich, Mateu Espasa, Isabel Sanfeliu, Juliana Esperalba, Miguel Fernández-Huerta, Margot P. Scheffer, Jaume Pinyol, Achilleas S. Frangakis, Maria Lluch-Senar, Shigetarou Mori, Keigo Shibayama, Tsuyoshi Kenri, Takayuki Kato, Keiichi Namba, Ignacio Fita, Makoto Miyata, David Aparicio
    Nature Communications, 2020
    Mycoplasma pneumoniae is a bacterial human pathogen that causes primary atypical pneumonia. M. pneumoniae motility and infectivity are mediated by the immunodominant proteins P1 and P40/P90, which form a transmembrane adhesion complex. Here we report the structure of P1, determined by X-ray crystallography and cryo-electron microscopy, and the X-ray structure of P40/P90. Contrary to what had been suggested, the binding site for sialic acid was found in P40/P90 and not in P1. Genetic and clinical variability concentrates on the N-terminal domain surfaces of P1 and P40/P90. Polyclonal antibodies generated against the mostly conserved C-terminal domain of P1 inhibited adhesion of M. pneumoniae, and serology assays with sera from infected patients were positive when tested against this C-terminal domain. P40/P90 also showed strong reactivity against human infected sera. The architectural elements determined for P1 and P40/P90 open new possibilities in vaccine development against M. pneumoniae infections.
  • Alternative conformation of the C-domain of the P140 protein from Mycoplasma genitalium
    David Vizarraga, Rosa Pérez-Luque, Jesús Martín, Ignacio Fita, David Aparicio
    Acta Crystallographica Section F Structural Biology Communications, 2020
    The human pathogen Mycoplasma genitalium is responsible for urethritis in men, and for cervicitis and pelvic inflammatory disease in women. The adherence of M. genitalium to host target epithelial cells is mediated through an adhesion complex called Nap, which is essential for infectivity. Nap is a transmembrane dimer of heterodimers of the immunodominant proteins P110 and P140. The M. genitalium genome contains multiple copies of portions that share homology with the extracellular regions of P140 and P110 encoded by the genes mg191 and mg192, respectively. Homologous recombination between the genes and the copies allows the generation of a large diversity of P140 and P110 variants to overcome surveillance by the host immune system. Interestingly, the C-terminal domain (C-domain) of the extracellular region of P140, which is essential for the function of Nap by acting as a flexible stalk anchoring the protein to the mycoplasma membrane, presents a low degree of sequence variability. In the present work, the X-ray crystal structures of two crystal forms of a construct of the P140 C-domain are reported. In both crystal forms, the construct forms a compact octamer with D4 point-group symmetry. The structure of the C-domain determined in this work presents significant differences with respect to the structure of the C-domain found recently in intact P140. The structural plasticity of the C-domain appears to be a possible mechanism that may help in the functioning of the mycoplasma adhesion complex.

RECENT SCHOLAR PUBLICATIONS

  • In silico design of stable single-domain antibodies with high affinity
    Z Zhang, R van der Kant, I Marković, D Vizarraga, T Garcia, K Maragkou, ...
    Structure , 2026
    2026
    Citations: 4
  • Sources of essential lipids for Mycoplasma pneumoniae via P116 to target liver and atherosclerotic lesions
    D Vizarraga, M Marcos, N Rotllan, J Martín, D Santos, M Camacho, B Soto, ...
    Nature Communications 16 (1), 11159 , 2025
    2025
  • Landscape of lipid uptake for the essential protein P116 of the human pathogen mycoplasma pneumoniae: Implications for tropism to atherosclerotic plaques
    N Rotllan, D Vizarraga, M Marcos, J Martín, D Santos, M Camacho, ...
    Atherosclerosis 407 , 2025
    2025
  • Artificial intelligence and first‐principle methods in protein redesign: A marriage of convenience?
    D Cianferoni, D Vizarraga, AM Fernández‐Escamilla, I Fita, R Hamdani, ...
    Protein Science 34 (8), e70210 , 2025
    2025
    Citations: 3
  • Nucleotides and amino-acids sequences corresponding to the Heavy and the (two) Light chains from Mab P1/MCA4 [Dataset]
    D Vizarraga, A Kawamoto, M Marcos-Silva, J Martín, F Makino, T Miyata, ...
    Plos One , 2025
    2025
  • Monoclonal/polyclonal antibodies inhibition assays (extended data)[Dataset]
    D Vizarraga, A Kawamoto, M Marcos-Silva, J Martín, F Makino, T Miyata, ...
    Plos One , 2025
    2025
  • Microcinematography of M. pneumoniae cells in in the presence of P40/P90 ectodomain polyclonal antisera [Dataset]
    D Vizarraga, A Kawamoto, M Marcos-Silva, J Martín, F Makino, T Miyata, ...
    Plos One , 2025
    2025
  • Analysis by MALS of samples containing Mab P1/MCA4 and the C-domain constructs from P1 [Dataset]
    D Vizarraga, A Kawamoto, M Marcos-Silva, J Martín, F Makino, T Miyata, ...
    Plos One , 2025
    2025
  • SDS-PAGE with protein extracts from M. genitalium mutant strains [Dataset]
    D Vizarraga, A Kawamoto, M Marcos-Silva, J Martín, F Makino, T Miyata, ...
    Plos One , 2025
    2025
  • Docking calculations on the binding interface between the Fab and the C-domain of P1 [Dataset]
    D Vizarraga, A Kawamoto, M Marcos-Silva, J Martín, F Makino, T Miyata, ...
    Plos One , 2025
    2025
  • Primers used for P1 and P40/P90 protein constructs expression [Dataset]
    D Vizarraga, A Kawamoto, M Marcos-Silva, J Martín, F Makino, T Miyata, ...
    Plos One , 2025
    2025
  • Western blotting analysis performed using Mab P1/MCA4 and different constructs from P1 (M. pneumoniae) and from P140 (M. genitalium)[Dataset]
    D Vizarraga, A Kawamoto, M Marcos-Silva, F Makino, T Miyata, ...
    Plos One , 2025
    2025
  • Primers used in the generation of M. genitalium adhesins constructs [Dataset]
    D Vizarraga, A Kawamoto, M Marcos-Silva, J Martín, F Makino, T Miyata, ...
    Plos One , 2025
    2025
  • C-domain of P1 movements during the “open” to “closed” transition [Dataset]
    D Vizarraga, A Kawamoto, M Marcos-Silva, J Martín, F Makino, T Miyata, ...
    Plos One , 2025
    2025
  • Quantification of the frequency of cells with multiple terminal organelles (mTO) and cells with no terminal organelle for each strain [Dataset]
    D Vizarraga, A Kawamoto, M Marcos-Silva, J Martín, F Makino, T Miyata, ...
    Plos One , 2025
    2025
  • Engelman motif mutants obtained [Dataset]
    D Vizarraga, A Kawamoto, M Marcos-Silva, J Martín, F Makino, T Miyata, ...
    Plos One , 2025
    2025
  • Cryo-EM data collection of the P1-Fab complex and model refinement of the P1-Fab complex [Dataset]
    D Vizarraga, A Kawamoto, M Marcos-Silva, J Martín, F Makino, T Miyata, ...
    Plos One , 2025
    2025
  • Antibodies used in this work [Dataset]
    D Vizarraga, A Kawamoto, M Marcos-Silva, J Martín, F Makino, T Miyata, ...
    Plos One , 2025
    2025
  • Immunolabeling for the localization of the Nap complexes in M. genitalium WT and MutE1-E2-E3 cells [Dataset]
    D Vizarraga, A Kawamoto, M Marcos-Silva, J Martín, F Makino, T Miyata, ...
    Plos One , 2025
    2025
  • The attachment and detachment cycle of the Nap complex [Dataset]
    D Vizarraga, A Kawamoto, M Marcos-Silva, J Martín, F Makino, T Miyata, ...
    Plos One , 2025
    2025

MOST CITED SCHOLAR PUBLICATIONS

  • Immunodominant proteins P1 and P40/P90 from human pathogen Mycoplasma pneumoniae
    D Vizarraga, A Kawamoto, U Matsumoto, R Illanes, R Pérez-Luque, ...
    Nature communications 11 (1), 5188 , 2020
    2020.0
    Citations: 80
  • Structure and mechanism of the Nap adhesion complex from the human pathogen Mycoplasma genitalium
    D Aparicio, MP Scheffer, M Marcos-Silva, D Vizarraga, L Sprankel, ...
    Nature communications 11 (1), 2877 , 2020
    2020.0
    Citations: 35
  • Essential protein P116 extracts cholesterol and other indispensable lipids for Mycoplasmas
    L Sprankel, D Vizarraga, J Martín, S Manger, J Meier-Credo, M Marcos, ...
    Nature structural & molecular biology 30 (3), 321-329 , 2023
    2023.0
    Citations: 27
  • The sialoglycan binding adhesins of Mycoplasma genitalium and Mycoplasma pneumoniae
    D Vizarraga, S Torres-Puig, D Aparicio, OQ Pich
    Trends in microbiology 29 (6), 477-481 , 2021
    2021.0
    Citations: 24
  • Immunodominant proteins P1 and P40/P90 from human pathogen Mycoplasma pneumoniae. Nat Commun 11: 5188
    D Vizarraga, A Kawamoto, U Matsumoto, R Illanes, R Pérez-Luque, ...
    2020.0
    Citations: 5
  • Immunodominant proteins P1 and P40/P90 from human pathogen Mycoplasma pneumoniae. Nat Commun. 2020; 11 (1): 5188
    D Vizarraga, A Kawamoto, U Matsumoto, R Illanes, R Perez-Luque, ...
    Epub 2020/10/16. https://doi. org/10.1038/s41467-020-18777-y PMID: 33057023 , 0
    Citations: 5
  • In silico design of stable single-domain antibodies with high affinity
    Z Zhang, R van der Kant, I Marković, D Vizarraga, T Garcia, K Maragkou, ...
    Structure , 2026
    2026.0
    Citations: 4
  • Dynamics of the adhesion complex of the human pathogens Mycoplasma pneumoniae and Mycoplasma genitalium
    D Vizarraga, A Kawamoto, M Marcos-Silva, J Martín, F Makino, T Miyata, ...
    PLoS Pathogens 21 (3), e1012973 , 2025
    2025.0
    Citations: 4
  • De novo design of high-affinity single-domain antibodies
    R Van Der Kant, Z Zhang, I Marković, D Vizarraga, T Garcia, K Maragkou, ...
    2024.0
    Citations: 4
  • Artificial intelligence and first‐principle methods in protein redesign: A marriage of convenience?
    D Cianferoni, D Vizarraga, AM Fernández‐Escamilla, I Fita, R Hamdani, ...
    Protein Science 34 (8), e70210 , 2025
    2025.0
    Citations: 3
  • Physiological sources of essential lipids for Mycoplasma pneumoniae via protein P116: Innovative biotechnological tools for targeting atherosclerotic and hepatic lesions
    JC Escola-Gil, D Vizarraga, M Marcos-Silva, N Rotllan, J Martín, D Santos, ...
    2025.0
    Citations: 3
  • Molecular basis of bacterial lectin recognition of eukaryotic glycans: The case of Mycoplasma pneumoniae and Mycoplasma genitalium cytoadhesins
    A Marseglia, MC Forgione, M Marcos-Silva, C Di Carluccio, Y Manabe, ...
    International journal of biological macromolecules 279, 135277 , 2024
    2024.0
    Citations: 3
  • Alternative conformation of the C-domain of the P140 protein from Mycoplasma genitalium
    D Vizarraga, R Pérez-Luque, J Martín, I Fita, D Aparicio
    Structural Biology and Crystallization Communications 76 (11), 508-516 , 2020
    2020.0
    Citations: 3
  • Estructura y función de las adhesinas de micoplasma del grupo Pneumoniae
    D Vizarraga
    IBMB (CSIC) , 2021
    2021.0
    Citations: 1
  • Sources of essential lipids for Mycoplasma pneumoniae via P116 to target liver and atherosclerotic lesions
    D Vizarraga, M Marcos, N Rotllan, J Martín, D Santos, M Camacho, B Soto, ...
    Nature Communications 16 (1), 11159 , 2025
    2025.0
  • Landscape of lipid uptake for the essential protein P116 of the human pathogen mycoplasma pneumoniae: Implications for tropism to atherosclerotic plaques
    N Rotllan, D Vizarraga, M Marcos, J Martín, D Santos, M Camacho, ...
    Atherosclerosis 407 , 2025
    2025.0
  • Nucleotides and amino-acids sequences corresponding to the Heavy and the (two) Light chains from Mab P1/MCA4 [Dataset]
    D Vizarraga, A Kawamoto, M Marcos-Silva, J Martín, F Makino, T Miyata, ...
    Plos One , 2025
    2025.0
  • Monoclonal/polyclonal antibodies inhibition assays (extended data)[Dataset]
    D Vizarraga, A Kawamoto, M Marcos-Silva, J Martín, F Makino, T Miyata, ...
    Plos One , 2025
    2025.0
  • Microcinematography of M. pneumoniae cells in in the presence of P40/P90 ectodomain polyclonal antisera [Dataset]
    D Vizarraga, A Kawamoto, M Marcos-Silva, J Martín, F Makino, T Miyata, ...
    Plos One , 2025
    2025.0
  • Analysis by MALS of samples containing Mab P1/MCA4 and the C-domain constructs from P1 [Dataset]
    D Vizarraga, A Kawamoto, M Marcos-Silva, J Martín, F Makino, T Miyata, ...
    Plos One , 2025
    2025.0