Tomas Malinauskas
Contact information
https://orcid.org/0000-0002-4847-5529
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, 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.
Please note that I left Oxford at the end of 2025 and am now working at the MRC Laboratory of Molecular Biology in Cambridge. My new email address is tomasm@mrc-lmb.cam.ac.uk
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
Protein Target Highlights in CASP16 : Insights From the Structure Providers
Journal article
Alexander LT. et al, (2026), Proteins: Structure, Function, and Bioinformatics, 94, 25 - 50
Mechanism of NACHO-mediated assembly of pentameric ligand-gated ion channels
Preprint
Hooda Y. et al, (2024)
Structural insights into Frizzled3 through nanobody modulators
Journal article
Hillier J. et al, (2024), Nature Communications, 15
Molecular mechanism of BMP signal control by Twisted gastrulation
Journal article
Malinauskas T. et al, (2024), Nature Communications, 15
GluD1 binds GABA and controls inhibitory plasticity
Journal article
Piot L. et al, (2023), Science, 382, 1389 - 1394
The molecular basis of drug selectivity for α5 subunit-containing GABAA receptors
Journal article
Kasaragod VB. et al, (2023), Nature Structural & Molecular Biology, 30, 1936 - 1946
A second update on mapping the human genetic architecture of COVID-19
Journal article
Kanai M. et al, (2023), Nature, 621, E7 - E26
Author Correction: GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19
Journal article
Pairo-Castineira E. et al, (2023), Nature, 619, E61 - E61
GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19
Journal article
Pairo-Castineira E. et al, (2023), Nature, 617, 764 - 768
Continuous population-level monitoring of SARS-CoV-2 seroprevalence in a large European metropolitan region
Journal article
Emmenegger M. et al, (2023), iScience, 26, 105928 - 105928
Human leukocyte antigen alleles associate with COVID-19 vaccine immunogenicity and risk of breakthrough infection
Journal article
Mentzer AJ. et al, (2023), Nature Medicine, 29, 147 - 157
Whole-genome sequencing reveals host factors underlying critical COVID-19
Journal article
Kousathanas A. et al, (2022), Nature, 607, 97 - 103
Differential assembly diversifies GABAA receptor structures and signalling
Journal article
Sente A. et al, (2022), Nature, 604, 190 - 194
Hedgehog-Interacting Protein is a multimodal antagonist of Hedgehog signalling
Journal article
Griffiths SC. et al, (2021), Nature Communications, 12
Anti-prothrombin autoantibodies enriched after infection with SARS-CoV-2 and influenced by strength of antibody response against SARS-CoV-2 proteins
Journal article
Emmenegger M. et al, (2021), PLOS Pathogens, 17, e1010118 - e1010118
Structure dynamics of HIV-1 Env trimers on native virions engaged with living T cells
Journal article
Carlon-Andres I. et al, (2021), Communications Biology, 4
Whole genome sequencing identifies multiple loci for critical illness caused by COVID-19
Preprint
Kousathanas A. et al, (2021)
Site-Specific Steric Control of SARS-CoV-2 Spike Glycosylation
Journal article
Allen JD. et al, (2021), Biochemistry, 60, 2153 - 2169
Simultaneous binding of Guidance Cues NET1 and RGM blocks extracellular NEO1 signaling
Journal article
Robinson RA. et al, (2021), Cell, 184, 2103 - 2120.e31
Site-specific steric control of SARS-CoV-2 spike glycosylation.
Journal article
Allen JD. et al, (2021), bioRxiv
Author Correction: Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2
Journal article
Huo J. et al, (2021), Nature Structural & Molecular Biology, 28, 326 - 326
A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses
Journal article
Tan TK. et al, (2021), Nature Communications, 12
Single-particle cryo-EM at atomic resolution
Journal article
Nakane T. et al, (2020), Nature, 587, 152 - 156
Author Correction: Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2
Journal article
Huo J. et al, (2020), Nature Structural & Molecular Biology, 27, 1094 - 1094
Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient
Journal article
Zhou D. et al, (2020), Nature Structural & Molecular Biology, 27, 950 - 958
Glypicans shield the Wnt lipid moiety to enable signalling at a distance
Journal article
McGough IJ. et al, (2020), Nature, 585, 85 - 90
Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike
Journal article
Huo J. et al, (2020), Cell Host & Microbe, 28, 445 - 454.e6
Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2
Journal article
Huo J. et al, (2020), Nature Structural & Molecular Biology, 27, 846 - 854
Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike
Journal article
Huo J. et al, (2020), Cell Host & Microbe, 28, 497 - 497
Repulsive guidance molecules lock growth differentiation factor 5 in an inhibitory complex
Journal article
Malinauskas T. et al, (2020), Proceedings of the National Academy of Sciences, 117, 15620 - 15631
R-spondins engage heparan sulfate proteoglycans to potentiate WNT signaling
Journal article
Dubey R. et al, (2020), eLife, 9
The morphogen Sonic hedgehog inhibits its receptor Patched by a pincer grasp mechanism
Journal article
Rudolf AF. et al, (2019), Nature Chemical Biology, 15, 975 - 982
Diversity of oligomerization in Drosophila semaphorins suggests a mechanism of functional fine-tuning
Journal article
Rozbesky D. et al, (2019), Nature Communications, 10
Author Correction: GABAA receptor signalling mechanisms revealed by structural pharmacology
Journal article
Masiulis S. et al, (2019), Nature, 566, E8 - E8
GABAA receptor signalling mechanisms revealed by structural pharmacology
Journal article
Masiulis S. et al, (2019), Nature, 565, 454 - 459
Cryo-EM structure of the human α1β3γ2 GABAA receptor in a lipid bilayer
Journal article
Laverty D. et al, (2019), Nature, 565, 516 - 520
Calcium-sensing receptor residues with loss- and gain-of-function mutations are located in regions of conformational change and cause signalling bias
Journal article
Gorvin CM. et al, (2018), Human Molecular Genetics, 27, 3720 - 3733
Heteromeric GABA A receptor structures in positively-modulated active states
Journal article
Miller PS. et al, (2018)
A calcium-sensing receptor mutation causing hypocalcemia disrupts a transmembrane salt bridge to activate β-arrestin–biased signaling
Journal article
Gorvin CM. et al, (2018), Science Signaling, 11
Structural Basis for Growth Differentiation Factor 5 (GDF5) Signaling Inhibition by Repulsive Guidance Molecules (RGMs)
Conference paper
Malinauskas T. et al, (2018), BIOPHYSICAL JOURNAL, 114, 464A - 464A
A Calcium-Sensing Receptor (CASR) Mutation Causes Hypocalcemia by Disrupting a Transmembrane Salt Bridge that Modulates β-arrestin Signaling.
Conference paper
Gorvin C. et al, (2017), JOURNAL OF BONE AND MINERAL RESEARCH, 32, S133 - S133
Structural Basis for Plexin Activation and Regulation
Journal article
Kong Y. et al, (2016), Neuron, 91, 548 - 560
Production of Heteromeric Transmembrane Receptors with Defined Subunit Stoichiometry
Journal article
Malinauskas T. and Furukawa H., (2016), Structure, 24, 1008 - 1009
Production of Heteromeric Transmembrane Receptors with Defined Subunit Stoichiometry
Journal article
Malinauskas T. and Furukawa H., (2016), Structure, 24, 653 - 655
Tailoring a Combination Preerythrocytic Malaria Vaccine
Journal article
Bauza K. et al, (2016), Infection and Immunity, 84, 622 - 634
Next generation sequencing reveals a novel mutation in the XY-linker region of phospholipase C zeta (PLCζ), resulting in truncated protein and oocyte activation deficiency
Conference paper
Amdani SN. et al, (2016), HUMAN REPRODUCTION, 31, 170 - 170
Genetic Control over mtDNA and Its Relationship to Major Depressive Disorder
Journal article
Cai N. et al, (2015), Current Biology, 25, 3170 - 3177
Application of whole genome and RNA sequencing to investigate the genomic landscape of common variable immunodeficiency disorders
Journal article
van Schouwenburg PA. et al, (2015), Clinical Immunology, 160, 301 - 314
Extracellular modulators of Wnt signalling
Journal article
Malinauskas T. and Jones EY., (2014), Current Opinion in Structural Biology, 29, 77 - 84
Genomes and phenomes of a population of outbred rats and its progenitors
Journal article
Baud A. et al, (2014), Scientific Data, 1
Structural insights into the inhibition of Wnt signaling by cancer antigen 5T4/Wnt-activated inhibitory factor 1
Journal article
Zhao Y. et al, (2014), Structure, 22, 612 - 620
Structural Insights into the Inhibition of Wnt Signaling by Cancer Antigen 5T4/Wnt-Activated Inhibitory Factor 1
Journal article
Zhao Y. et al, (2014), Structure, 22, 612 - 620
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
Journal article
Bauza K. et al, (2014), Infection and Immunity, 82, 1277 - 1286
Structure and function of the Smoothened extracellular domain in vertebrate Hedgehog signaling
Journal article
Nachtergaele S. et al, (2013), eLife, 2
Structural insights into proteoglycan-shaped Hedgehog signaling
Journal article
Whalen DM. et al, (2013), Proceedings of the National Academy of Sciences, 110, 16420 - 16425
Combined sequence-based and genetic mapping analysis of complex traits in outbred rats
Journal article
(2013), Nature Genetics, 45, 767 - 775