Group Leader



Structural Biology of Host-Pathogen Interactions Group


The Structural Biology of Host-Pathogen Interactions group focuses in the understanding of the protein-protein interactions that mediate the communication between human beings and the bacterial communities to which we are continuously exposed. These interactions often involve bacterial pathogens, which attempt to evade the constant surveillance of human innate immunity and, specifically, the activated branch of the complement system. Our group studies other processes that are vital for bacterial cell survival in the human body as well as in environmental pools, including enzymes of the sugar and amino acid metabolism and sulfur mobilisation and trafficking. To this aim, we use a combination of advanced protein production techniques, X-ray diffraction, biochemical, biophysical, and computational chemistry methods to analyse snapshots of the protein complex interactions as well as their associated dynamic behavior, both of which underlie the functional outcomes of those interactions.

As a result of our participation in the European ComplexINC consortium, we have recently co-founded a start-up biopharmaceutical company, Abvance, to deliver innovative antibody-based medicines for the treatment of immune disorders, inflammatory and neurodegenerative diseases.

Host-Pathogen interactions and the innate immunity

The interactions that occur at the interface between the human host and the myriad bacterial microorganisms with which we come into daily contact constitute a topic of profound significance, both at a fundamental biological level and as an area of expanding medical interest. The complement system of the innate immunity stands as one of the first defence barriers against pathogens. It is a collection of soluble and membrane-associated proteins that monitor the blood and tissue interstitial fluids for pathogens, apoptotic cells and immune complexes. Pathogens have evolved sophisticated molecular weaponry that allows them to escape surveillance from the complement system, a strategy designated as immunoevasion. In this context, we are focused in elucidating the structures and mechanistic details of the complement system components and their protein complexes with virulence factors with immunoevasive properties. Increasing our understanding of these processes at the atomic level is crucial to develop potential treatments against many diseases.

Superposition of A. vaginae and human liver GAPDH X-ray structures

Sulfur trafficking and tRNA hypermodifications

Across all domains of life, organisms have evolved complex systems of interacting proteins with the task of mobilising sulfur atoms from the amino acid L-cysteine in the form of highly reactive persulfides (-S-S), which are then channeled to other proteins until they reach their ultimate destination — iron-sulfur (Fe-S) clusters, sulfur-containing vitamins, cofactors and lipids, or thiol-containing tRNA hypermodified ribonucleosides. Our research has focused on the minimalistic CSD (Cysteine Sulfinate Desulfinase) system of the model bacterium E. coli, which encodes a cysteine desulfurase (CsdA), a sulfur acceptor (CsdE), and TcdA, an E1-like enzyme capable of cyclising the N6-threonylcarbamoyl adenosine (t6A) present at the A37 position of the anti-codon stem loop (ASL) motif of tRNA(ANN) molecules.

We have determined the crystal structures of all three component proteins in order to understand their function. The recent crystal structure of a doubly persulfided CsdA-CsdE complex was central to our proposal of a novel mechanism for the transfer of sulfur atoms across protein-protein interfaces and to deciphering the role of conserved Cys loop motifs present both in CsdA and in SufS.

The connection with tRNA biology is made through TcdA, the enzyme responsible for the synthesis of "cyclic t6A" (ct6A) in bacteria, protists, fungi and plants, where it ensures the fidelity and efficiency of translation. We have investigated the structure of TcdA both in free form and associated with tRNA using a combination of X-ray crystallography/SAXS and other techniques, which represents one first step toward deciphering the biological role of this intriguing enzyme.

TcdA-tRNA Complex

Carbohydrate active and sugar metabolic enzymes

Carbohydrate active enzymes are enzymes capable of synthesising or breaking glycosidic bonds as well as the non-catalytic carbohydrate binding modules (CBMs) that frequently are associated with the active enzymes. Sugar metabolic enzyme is a wider term describing any enzyme which recognises, binds and modifies sugar molecules, usually within the context of a biochemical pathway. Carbohydrate active and sugar metabolic enzymes are also relevant enzymes for biotechnological applications, including the biofuel industry, as well as for the analysis of plant-fungi interactions owing to the widespread use of extracellular glycosyl hydrolases by plant pathogenic fungi.

Improving Methods for Production of Therapeutic Molecules

We are interested in the development and improvement of new technologies and production tools for complex protein biologics using yeast expression methodologies and other eukaryotic expression systems. Our group was a member of the FP7 Project ComplexINC, which conceptualised and systematically generated advanced toolkits to enable high-throughput assembly of complex biologics and metabolic pathways using eukaryotic expression systems. The ultimate goal of these toolkits, including two yeast-based toolkits developed in our laboratory, was enabling micro- and large-scale production of high-quality protein biologics for drug discovery and as biotherapeutics.


Fernández FJ, Gómez S, Navas-Yuste S, López-Estepa M, Vega MC  [2017]. Protein-tRNA Agarose Gel Retardation Assays for the Analysis of the N6-threonylcarbamoyladenosine TcdA Function. J Vis Exp 124.

Querol-García J, Fernández FJ, Marin AV, Gómez S, Fullà D, Melchor-Tafur C, Franco-Hidalgo V, Albertí S, Juanhuix J, Rodríguez de Córdoba S, Regueiro JR, Vega MC.  [2017]. Crystal Structure of Glyceraldehyde-3-Phosphate Dehydrogenase from the Gram-Positive Bacterial Pathogen A. vaginae, an Immunoevasive Factor that Interacts with the Human C5a Anaphylatoxin. Front Microbiol 8:541.

MC Vega, Fernández FJ, Berger I  [2016]. Advanced Technologies for Protein Complex production and Characterization. Preface. Adv Exp Med Biol. 2016;896:v-vii.

Gómez S, López-Estepa M, Fernández FJ, Vega MC  [2016]. Protein Complex production in Alternative Prokaryotic Hosts. Adv Exp Med Biol. 2016;896:115-33.

Fernández FJ, López-Estepa M, Querol-García J, Vega MC  [2016]. Production of Protein Complexes in Non-methylotrophic and Methylotrophic Yeasts. Adv Exp Med Biol. 2016;896:137-53.

Gómez S, López-Estepa M, Fernández FJ, Suárez T, Vega MC  [2016]. Alternative Eukaryotic Expression Systems for the Production of Proteins and Protein Complexes. Adv Exp Med Biol. 2016;896:167-84.

Fernández FJ, Vega MC  [2016]. Choose a Suitable Expression Host: A survey of Available Protein Production Platforms. Adv Exp Med Biol. 2016;896:15-24.

Gómez S, Fernández FJ, Vega MC  [2016]. Heterologous Expression of Proteins in Aspergillus. New and Future Developments in Microbial Biotechnology and Bioengineering. 55-68.

Gómez S, Payne AM, Savko M, Fox GC, Shepard WE, Fernández FJ, Vega MC  [2016]. Structural and functional characterization of a highly stable endo-β-1,4-xylanase from Fusarium oxysporum and its development as an efficient immobilized biocatalyst. Biotechnology for Biofuels 9:191.

Fernández FJ, Ardá A, López-Estepa M, Aranda J, Peña-Soler E, Garces F, Round A, Campos-Olivas R, Bruix M, Coll M, Tuñón I, Jiménez-Barbero J, and Vega MC  [2016]. Mechanism of Sulfur Transfer Across Protein-Protein Interfaces: The Cysteine Desulfurase Model System. ACS Catalysis 6(6), 3975-3984.



Healing complement C3-associated diseases (SAF2015-72961-EXP)
PI: M. Cristina Vega

Development of new glycostructures with anti-infectious activity: Gram-positive bacteria and Dengue virus (CTQ2015-66206-C2-2-R)
PI: M. Cristina Vega

Structural Biology of Host-Pathogen Interactions (20160E064)
CSIC, PIE Project
PI: M. Cristina Vega

New Technologies and Production Tools for Complex Protein Biologics (ComplexINC, 279039)
PI: M. Cristina Vega

Molecular structural basis of the dense deposit disease (DDD) caused by mutation in C3 and therapeutic opportunities (PI-121667)
PI: M. Cristina Vega

Biology and physiopathology of the complement system (S2010/BMD-2316)
Comunidad de Madrid

PI: M. Cristina Vega

National Research & Development Program Grant PET2008-0101 (Spanish Ministry of Science & Innovation). PI MC Vega (2009-2012).

National Research & Development Program GrantBFU2010-22260-C02-02 (Spanish Ministry of Science and Innovation). PI MC Vega (2011).

CSIC Start-up Grant 200820I056 (CSIC). PI MC Vega (2008-2009).

National Research & Development Program GrantBFU2006-15573 (Spanish Ministry of Science & Education). PI MC Vega (2007-2010).

ARCS Training and Mobility Action Grant ARCS1-00152 (Generalitat de Catalunya). PI MC Vega (2009).

Ramón y Cajal Program (Spanish Ministry of Science & Education). PI MC Vega (2004-2005).

CSIC          Gobierno de España          EU 7th Framework Programme          Comunidad de Madrid




Fellowships and jobs


More info


Vega, M. Cristina

B.Sc. 1992 in Organic Chemistry Dpt. of the Chemistry Faculty (UB) in Barcelona.

Ph.D. 1997 in Structural Biology from UPC and CID-CSIC in Barcelona.

Postdoctoral fellow at EMBL-Heidelberg and EMBL-Hamburg, Germany.

Ramón y Cajal scientist in 2004 at IBMB-CSIC.

Group Leader at CIB-CSIC since 2008.

Outreach activities

  • We have edited a new book on advanced methodologies for protein complex production using a variety of expression hosts and systems, which was published by Springer in spring of 2016. The volume, entitled Advanced Technologies for Protein Complex Production and Characterization (doi:10.1007/978-3-319-27216-0), belongs in the Advances in Experimental Medicine and Biology (v. 896), and was published by Springer in spring of 2016.


Advanced Technologies for Protein Complex Production and Characterization (2016 Springer Book)