Tomas Malinauskas
Contact information
tomas@strubi.ox.ac.uk
tomas.malinauskas@gmail.com
https://orcid.org/0000-0002-4847-5529
University of Oxford, Centre for Human Genetics, Roosevelt Drive, Oxford, OX3 7BN, United Kingdom
He/him/his
Research groups
Collaborators
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E. Yvonne Jones
The Sir Andrew McMichael Professor of Structural Immunology
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Loic Carrique
Senior CryoEM Staff Scientist
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Karl Harlos
Post Doctoral Research Associate
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Yuguang Zhao
Instruct Senior Scientist
Tomas Malinauskas
DPhil
Senior Postdoctoral Research Scientist
Structural biology of cell surface receptors
I am a structural biologist dedicated to unraveling the molecular mechanisms governing cell surface receptor signaling, with a particular emphasis on their implications for human health and disease. By employing X-ray crystallography and cryo-electron microscopy coupled with structure-guided biophysical and cellular assays, I have elucidated numerous receptor-ligand interactions and downstream signaling pathways throughout my career. My research focuses on signaling pathways orchestrating the development of all multicellular organisms (Wnt, Bone morphogenetic protein, and Hedgehog), neuron growth (Neogenin-Repulsive Guidance Molecules and Plexins-Semaphorins), and synaptic transmission (gamma-aminobutyric acid receptors). My aim is to shed light on disease mechanisms and identify innovative strategies for therapeutic intervention, ultimately striving to improve patient healthcare.
If you require a structural perspective for your project, please feel free to email me. I am happy to assist with anything from advising on protein constructs and expression to analyzing the structure-function relationship of the target protein (e.g., the impact of mutations), and creating structural figures and movies for your papers.
Main publications:
- Malinauskas, T.*, **, Moore, G.*, Rudolf, A.F.*, Eggington, H., Belnoue-Davis, H., El Omari, K., Griffiths, S.C., Woolley, R.E., Duman, R., Wagner, A., Leedham, S.J., Baldock, C., Ashe, H.L.**, and Siebold, C.**. Molecular Mechanism of BMP Signal Control by Twisted Gastrulation. Nat. Commun., 15 (1): 4976 (2024). * These authors contributed equally. ** Co-corresponding authors.
- Robinson, R.A.*, Griffiths, S.C.*, van de Haar*, L.L., Malinauskas, T.*, van Battum, E.Y., Zelina, P., Schwab, R.A., Karia, D., Malinauskaite, L., Brignani, S., van den Munkhof, M.H., Düdükcü, Ö., De Ruiter, A.A., Van den Heuvel, D.M.A., Bishop, B., Elegheert, J., Aricescu, A.R., Pasterkamp, R.J., and Siebold, C. Simultaneous binding of Guidance Cues NET1 and RGM blocks extracellular NEO1 signaling. Cell, 184 (8): 2103–2120 (2021). * These authors contributed equally.
- Malinauskas, T.*, Peer, T.V., Bishop, B., Mueller, T.D.*, and Siebold, C*. Repulsive Guidance Molecules lock Growth Differentiation Factor 5 in an inhibitory complex. Proc. Natl. Acad. Sci. U.S.A., 117 (27), 15620–15631 (2020). * Co-corresponding authors.
- Zhao, Y.*, Malinauskas, T.*, Harlos, K., and Jones, E.Y. Structural insights into the inhibition of Wnt signaling by cancer antigen 5T4/Wnt-activated inhibitory factor 1. Structure, 22 (4), 612–620 (2014). * These authors contributed equally.
- Janssen, B.J.C.*, Malinauskas, T.*, Weir, G.A., Cader, M.Z., Siebold, C., and Jones, E.Y. Neuropilins lock secreted semaphorins onto plexins in a ternary signalling complex. Nat. Struct. Mol. Biol., 19 (12), 1293–1299 (2012). * These authors contributed equally.
- Malinauskas, T., Aricescu, A.R., Lu, W., Siebold, C., and Jones, E.Y. Modular mechanism of Wnt signaling inhibition by Wnt inhibitory factor 1. Nat. Struct. Mol. Biol., 18 (8), 886–893 (2011).
Websites
Recent publications
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Mechanism of NACHO-mediated assembly of pentameric ligand-gated ion channels.
Hooda Y. et al, (2024)
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Structural insights into Frizzled3 through nanobody modulators.
Hillier J. et al, (2024), Nat Commun, 15
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GluD1 binds GABA and controls inhibitory plasticity.
Piot L. et al, (2023), Science (New York, N.Y.)
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The molecular basis of drug selectivity for α5 subunit-containing GABAA receptors.
Kasaragod VB. et al, (2023), Nature structural & molecular biology
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A second update on mapping the human genetic architecture of COVID-19.
COVID-19 Host Genetics Initiative None., (2023), Nature, 621, E7 - E26
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Author Correction: GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19.
Pairo-Castineira E. et al, (2023), Nature
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GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19.
Pairo-Castineira E. et al, (2023), Nature
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Continuous population-level monitoring of SARS-CoV-2 seroprevalence in a large European metropolitan region
Emmenegger M. et al, (2023), iScience, 26, 105928 - 105928
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Human leukocyte antigen alleles associate with COVID-19 vaccine immunogenicity and risk of breakthrough infection
Mentzer AJ. et al, (2023), Nature Medicine, 29, 147 - 157
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Whole-genome sequencing reveals host factors underlying critical COVID-19.
Kousathanas A. et al, (2022), Nature, 607, 97 - 103
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Differential assembly diversifies GABAA receptor structures and signalling.
Sente A. et al, (2022), Nature, 604, 190 - 194
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Hedgehog-Interacting Protein is a multimodal antagonist of Hedgehog signalling
Griffiths SC. et al, (2021), Nature Communications, 12
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Anti-prothrombin autoantibodies enriched after infection with SARS-CoV-2 and influenced by strength of antibody response against SARS-CoV-2 proteins.
Emmenegger M. et al, (2021), PLoS pathogens, 17
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A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses
Tan TK. et al, (2021), Nature Communications, 12
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Structure dynamics of HIV-1 Env trimers on native virions engaged with living T cells.
Carlon-Andres I. et al, (2021), Communications biology, 4
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Whole genome sequencing identifies multiple loci for critical illness caused by COVID-19
Kousathanas A. et al, (2021)
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Site-Specific Steric Control of SARS-CoV-2 Spike Glycosylation.
Allen JD. et al, (2021), Biochemistry, 60, 2153 - 2169
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Simultaneous binding of Guidance Cues NET1 and RGM blocks extracellular NEO1 signaling
Robinson RA. et al, (2021), Cell, 184, 2103 - 2120.e31
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Site-specific steric control of SARS-CoV-2 spike glycosylation.
Allen JD. et al, (2021), bioRxiv
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Author Correction: Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2
Huo J. et al, (2021), Nature Structural & Molecular Biology, 28, 326 - 326
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Author Correction: Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2
Huo J. et al, (2020), Nature Structural & Molecular Biology, 27, 1094 - 1094
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Single-particle cryo-EM at atomic resolution.
Nakane T. et al, (2020), Nature, 587, 152 - 156
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Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient
Zhou D. et al, (2020), Nature Structural & Molecular Biology, 27, 950 - 958
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Glypicans shield the Wnt lipid moiety to enable signalling at a distance.
McGough IJ. et al, (2020), Nature, 585, 85 - 90
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Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike
Huo J. et al, (2020), Cell Host & Microbe, 28, 445 - 454.e6
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Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike
Huo J. et al, (2020), Cell Host & Microbe, 28, 497 - 497
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Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2
Huo J. et al, (2020), Nature Structural & Molecular Biology, 27, 846 - 854
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A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses
Tan TK. et al, (2020)
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Repulsive guidance molecules lock growth differentiation factor 5 in an inhibitory complex.
Malinauskas T. et al, (2020), Proceedings of the National Academy of Sciences of the United States of America, 117, 15620 - 15631
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Single-particle cryo-EM at atomic resolution
Nakane T. et al, (2020)
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R-spondins engage heparan sulfate proteoglycans to potentiate WNT signaling.
Dubey R. et al, (2020), eLife, 9
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Diversity of oligomerization in Drosophila semaphorins suggests a mechanism of functional fine-tuning
Rozbesky D. et al, (2019), Nature Communications, 10
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The morphogen Sonic hedgehog inhibits its receptor Patched by a pincer grasp mechanism.
Rudolf AF. et al, (2019), Nature chemical biology, 15, 975 - 982
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Author Correction: GABAA receptor signalling mechanisms revealed by structural pharmacology.
Masiulis S. et al, (2019), Nature, 566
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Cryo-EM structure of the human α1β3γ2 GABAA receptor in a lipid bilayer.
Laverty D. et al, (2019), Nature, 565, 516 - 520
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GABAA receptor signalling mechanisms revealed by structural pharmacology.
Masiulis S. et al, (2019), Nature, 565, 454 - 459
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Calcium-sensing receptor residues with loss- and gain-of-function mutations are located in regions of conformational change and cause signalling bias
Gorvin CM. et al, (2018), Human Molecular Genetics, 27, 3720 - 3733
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Heteromeric GABAAreceptor structures in positively-modulated active states
Miller PS. et al, (2018)
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A calcium-sensing receptor mutation causing hypocalcemia disrupts a transmembrane salt bridge to activate β-arrestin–biased signaling
Gorvin CM. et al, (2018), Science Signaling, 11
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Structural Basis for Growth Differentiation Factor 5 (GDF5) Signaling Inhibition by Repulsive Guidance Molecules (RGMs)
Malinauskas T. et al, (2018), BIOPHYSICAL JOURNAL, 114, 464A - 464A
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A Calcium-Sensing Receptor (CASR) Mutation Causes Hypocalcemia by Disrupting a Transmembrane Salt Bridge that Modulates beta-arrestin Signaling.
Gorvin C. et al, (2017), JOURNAL OF BONE AND MINERAL RESEARCH, 32, S133 - S133
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Structural Basis for Plexin Activation and Regulation
Kong Y. et al, (2016), Neuron, 91, 548 - 560
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Next generation sequencing reveals a novel mutation in the XY-linker region of phospholipase C zeta (PLC zeta), resulting in truncated protein and oocyte activation deficiency
Amdani SN. et al, (2016), HUMAN REPRODUCTION, 31, 170 - 170
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Production of Heteromeric Transmembrane Receptors with Defined Subunit Stoichiometry
Malinauskas T. and Furukawa H., (2016), Structure, 24, 1008 - 1009
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Production of Heteromeric Transmembrane Receptors with Defined Subunit Stoichiometry
Malinauskas T. and Furukawa H., (2016), Structure, 24, 653 - 655
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Tailoring a Combination Preerythrocytic Malaria Vaccine
Bauza K. et al, (2016), Infection and Immunity, 84, 622 - 634
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Genetic Control over mtDNA and Its Relationship to Major Depressive Disorder
Cai N. et al, (2015), Current Biology, 25, 3170 - 3177
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Application of whole genome and RNA sequencing to investigate the genomic landscape of common variable immunodeficiency disorders
van Schouwenburg PA. et al, (2015), Clinical Immunology, 160, 301 - 314
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Extracellular modulators of Wnt signalling
Malinauskas T. and Jones EY., (2014), Current Opinion in Structural Biology, 29, 77 - 84
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Genomes and phenomes of a population of outbred rats and its progenitors
Baud A. et al, (2014), Scientific Data, 1
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Structural insights into the inhibition of Wnt signaling by cancer antigen 5T4/Wnt-activated inhibitory factor 1
Zhao Y. et al, (2014), Structure, 22, 612 - 620
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Structural Insights into the Inhibition of Wnt Signaling by Cancer Antigen 5T4/Wnt-Activated Inhibitory Factor 1
Zhao Y. et al, (2014), Structure, 22, 612 - 620
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Efficacy of a Plasmodium vivax Malaria Vaccine Using ChAd63 and Modified Vaccinia Ankara Expressing Thrombospondin-Related Anonymous Protein as Assessed with Transgenic Plasmodium berghei Parasites
Bauza K. et al, (2014), Infection and Immunity, 82, 1277 - 1286
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Abstract
(2013)
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Structure and function of the Smoothened extracellular domain in vertebrate Hedgehog signaling
Nachtergaele S. et al, (2013), eLife, 2
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Structural insights into proteoglycan-shaped Hedgehog signaling
Whalen DM. et al, (2013), Proceedings of the National Academy of Sciences, 110, 16420 - 16425
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Combined sequence-based and genetic mapping analysis of complex traits in outbred rats
(2013), Nature Genetics, 45, 767 - 775
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Neuropilins Lock Secreted Semaphorins onto Plexins in a Ternary Signalling Complex
Malinauskas T. et al, (2013), Biophysical Journal, 104, 613a - 613a
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Neuropilins lock secreted semaphorins onto plexins in a ternary signaling complex
Janssen BJC. et al, (2012), Nature Structural & Molecular Biology, 19, 1293 - 1299
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Correction
(2012), Biophysical Journal, 102, 1468 - 1468
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High-throughput Molecular Docking Now in Reach for a Wider Biochemical Community
Balan DM. et al, (2012), 2012 20th Euromicro International Conference on Parallel, Distributed and Network-based Processing
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Modular Mechanism of Wnt Signalling Inhibition by Wnt Inhibitory Factor 1
Malinauskas T. et al, (2012), Biophysical Journal, 102, 518a - 518a
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Structural and Functional Studies of LRP6 Ectodomain Reveal a Platform for Wnt Signaling
Chen S. et al, (2011), Developmental Cell, 21, 848 - 861
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Modular mechanism of Wnt signaling inhibition by Wnt inhibitory factor 1
Malinauskas T. et al, (2011), Nature Structural & Molecular Biology, 18, 886 - 893
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Modular mechanism of Wnt signaling inhibition by Wnt inhibitory factor 1
Malinauskas T. et al, (2011), Nature Structural and Molecular Biology, 18, 886 - 893
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Docking of Fatty Acids into the WIF Domain of the Human Wnt Inhibitory Factor-1
Malinauskas T., (2008), Lipids, 43, 227 - 230
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Prussian blue-based amperometric sensor as a tool for the study of Pichia pastoris alcohol oxidase-catalyzed reactions
Malinauskas T. and Malinauskas A., (2005), BULLETIN OF ELECTROCHEMISTRY, 21, 289 - 295