Nico van Nuland
Biomolecular NMR
VIB Department of Molecular and Cellular Interactions, Vrije Universiteit Brussel

PhD : Universiteit Groningen, Groningen, The Netherlands, '94 Postdoc: Univ. of Oxford, Oxford, UK, '94-'96 Postdoc: Univ. Groningen, Groningen, The Netherlands, '96-'98 Postdoc: Univ. of Granada, Granada, Spain, '97-'99 Supervisor European NMR Large-scale Facility, Univ. Utrecht, Utrecht, The Netherlands, '00-'04 VIB Group leader as of 01/01/2009

e-mail phone +32 2 629 35 53 ADDRESS

Current team members
Group leader: Nico van Nuland
Staff scientist: Stéphanie Ramboarina
Postdoctoral scientists: Abel Garcia Pino, Oleksandr Volkov
Ph.D. Students: Lucía Rubio Fernàndez, Radu Huculeci

Keywords
NMR - molecular recognition - protein structure - folding and dynamics - protein-protein interactions

Science

A deep understanding of the rules governing molecular recognition processes is crucial to rational designing drugs and its pharmacological and biotechnological implications are noteworthy. For an in deep understanding of such processes, the elucidation of the complex interrelation among structure, dynamics and energetics becomes a must. Our research is dedicated to understanding this interrelationship by combining structural biology (X-ray crystallography and NMR) with thermodynamics. Our specific interest aims to increase the understanding of the fundamentals of biological processes such as protein folding-unfolding-misfolding and protein stability, but particularly that of protein-protein interactions, using primarily high-resolution NMR spectroscopy.
Our group has 3 main research topics:

1. Multiplicity of SH3 domains: Living cells feature complex protein networks involved in information signal transfer and processing events finely modulated by protein-protein interactions mediated often by small modular domains such as the SH3 domains. The incidence of different SH3 binding motifs on the same target protein may be an intricate mechanism used by the cell to regulate SH3-mediated interactions. Often, modular interaction domains also occur in tandem on regulatory proteins. The CIN85/CMS family of adaptor proteins contains three highly similar N-terminal SH3 domains that are involved in a wide variety of intermolecular interactions with different targets. It has been hypothesized that such regulatory proteins can increase their affinity and specificity through co-operative binding involving multiple domains of the same or different kinds. The research focuses on the effect of the presence of a second or third domain on the affinity and specificity of the binding of the former to its target. Moreover, recent research has shown that binding affinities change for both the SH2 as well as the SH3 domain of Fyn when either one of them is already linked to a peptide. Hence, to understand domain multiplicity one also has to investigate the mechanics of intra- and inter-domain communication. This investigation is performed in collaboration with Tom Lenaerts, former member of the Switch lab of the VIB, and is a continuation of previous research activities in collaboration with members of the University of Granada. The aimed research furthermore covers the combination of rapid injection techniques combined with rapid acquisition NMR methods for the analysis of (fast) kinetic processes.

2. Bacterial toxin-antitoxin (TA) modules (Project leader Remy Loris): Prokaryotes possess a series of tools to respond to sudden and chronic environmental stresses such as the presence of antibiotics or scarcity of food resources. Among these tools are the so-called toxin-antitoxin (TA) modules, small operons encoding a "toxin" and an "antitoxin" protein. TA toxins recognize their antitoxins via their intrinsically unfolded C-terminal domain, which becomes structured upon binding. These events have to be viewed in the wider perspective of the recognition of intrinsically unstructured binding partners, for which NMR is most suited. Study of the mechanisms and specificity determinants that govern these interactions will therefore also be relevant for the problem of protein folding in general.

3. DBL domains in Malaria (Project leader Stephanie Ramboarina): Adherence of Plasmodium falciparum infected erythrocytes to placenta of pregnant women leads to drastic damage and complication during pregnancy (placental malaria). P. falciparum erythrocyte membrane protein 1 (PfEMP1) VAR2CSA protein has been identified as the main adhesion, binding exclusively chondroitin sulfate A (CSA) on placenta. Nevertheless, VAR2CSA becomes the target of maternal antibodies after subsequent pregnancies suggesting this protein may be an important target of protective immunity making it the leading candidate for a pregnancy malaria vaccine. VAR2CSA is a large protein of 350 kDa with an extracellular part composed of six Duffy binding-like (DBL) domains of about 36 to 45 kDa. The main goal of this project is to decipher the mechanism of recognition of DBLs of VAR2CSA with glycosaminoglycans, such as CSA.

Announcement: Opening Ceremony and Inauguration Jean Jeener NMR Center - Friday, 7 May 2010, Brussels, Belgium

Ortega-Roldan J, Jensen M, Brutscher B, Azuaga A, Blackledge M, van Nuland N
Accurate characterization of weak macromolecular interactions by titration of NMR residual dipolar couplings: application to the CD2AP SH3-C:ubiquitin complex
NUCLEIC ACIDS RES 37, e70, 2009



Bernard C, Houben K, Derix N, Marks D, Van Der Horst M, Hellingwerf K, Boelens R, Kaptein R, Van Nuland N
The solution structure of a transient photoreceptor intermediate: Delta25 photoactive yellow protein
STRUCTURE 13, 953-62, 2005



Hsu S, Breukink E, Tischenko E, Lutters M, De Kruijff B, Kaptein R, Bonvin A, Van Nuland N
The nisin-lipid II complex reveals a pyrophosphate cage that provides a blueprint for novel antibiotics
NAT STRUCT MOL BIOL 11, 963-7, 2004



Canet D, Lyon C, Scheek R, Robillard G, Dobson C, Hore P, Van Nuland N
Rapid formation of non-native contacts during the folding of HPr revealed by real-time photo-CIDNP NMR and stopped-flow fluorescence experiments
J MOL BIOL 330, 397-407, 2003



Van Nuland N, Forge V, Balbach J, Dobson C
Real-time NMR studies of protein folding
ACCOUNTS CHEM RES 31, 773-780, 1998

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