Publications

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Bistable expression of a toxin-antitoxin system located in a cryptic prophage of Escherichia coliO157:H7 Vrije Universiteit Brussel

Dukas Jurenas, Nathan Fraikin, Frédéric Goormaghtigh, Pieter De Bruyn, Alexandra Vandervelde, Thomas Jove, Daniel Charlier, Remy Loris, Laurence Van Melderen
Type II toxin-antitoxin systems (TA) are classically composed of two genes encoding a toxic protein and a cognate antitoxin protein. Both genes are organized in an operon whose transcription is autoregulated at the level of transcription by the antitoxin-toxin complex thanks to the antitoxin DNA-binding domain. Here we investigated the transcriptional regulation of a particular toxin-antitoxin (TA) system located in the immunity region of a ...

The sequence-ensemble relationships in fuzzy protein complexes Vrije Universiteit Brussel

San Hadzi, Remy Loris, Jurij Lah
Intrinsically disordered proteins (IDPs) interact with globular proteins through variety of mechanisms, resulting in structurally heterogeneous ensembles known as fuzzy complexes. While there exists a reasonable comprehension on how IDP sequence determines the unbound IDP ensemble, little is known about what shapes the structural ensembles of IDPs bound to their targets. Using a statistical-thermodynamic model we show that the target-bound ...

Alternative dimerization is required for activity and inhibition of the HEPN ribonuclease RnlA Vrije Universiteit Brussel KU Leuven

Gabriela Garcia Rodriguez, Daniel Charlier, Dorien Wilmaerts, Jan Michiels, Remy Loris

The rnlAB toxin-antitoxin operon from Escherichia coli functions as an anti-phage defense system. RnlA was identified as a member of the HEPN (Higher Eukaryotes and Prokaryotes Nucleotide-binding domain) superfamily of ribonucleases. The activity of the toxin RnlA requires tight regulation by the antitoxin RnlB, the mechanism of which remains unknown. Here we show that RnlA exists in an equilibrium between two different homodimer states: an ...

Crystal and solution structure of NDRG1, a membrane-binding protein linked to myelination and tumour suppression Vrije Universiteit Brussel

Venla Mustonen, Gopinath Muruganandam, Remy Loris, Petri Kursula, Salla Ruskamo
N‐myc downstream‐regulated gene 1 (NDRG1) is a tumour suppressor involved in vesicular trafficking and stress response. NDRG1 participates in peripheral nerve myelination, and mutations in the NDRG1 gene lead to Charcot‐Marie‐Tooth neuropathy. The 43‐kDa NDRG1 is considered as an inactive member of the α/β hydrolase superfamily. In addition to a central α/β hydrolase fold domain, NDRG1 consists of a short N terminus and a C‐terminal region with ...

Prokaryote toxin-antitoxin modules: complex regulation of an unclear function Vrije Universiteit Brussel

Pieter De Bruyn, Yana Girardin, Remy Loris
Toxin-antitoxin (TA) modules are small operons in bacteria and archaea that encode a metabolic inhibitor (toxin) and a matching regulatory protein (antitoxin). While their biochemical activities are often well defined, their biological functions remain unclear. In type II TA modules, both toxin and antitoxin are proteins, and the antitoxin inhibits the biochemical activity of the toxin via complex formation with the toxin. The different TA ...

Arc self‐association and formation of virus‐like capsids are mediated by an N‐terminal helical coil motif Vrije Universiteit Brussel

Maria Eriksen, Oleksii Nikolaienko, Erik Hallin, Sverre Grødem, Helene Bustad, Marte Flydal, Ian Merski, Tomohisa Hosokawa, Daniela Lascu, Shreeram Akerkar, et al.

Activity-regulated cytoskeleton-associated protein (Arc) is a protein interaction hub with diverse roles in intracellular neuronal signaling, and important functions in neuronal synaptic plasticity, memory, and postnatal cortical development. Arc has homology to retroviral Gag protein and is capable of self-assembly into virus-like capsids implicated in the intercellular transfer of RNA. However, the molecular basis of Arc self-association ...

A nanobody toolbox targeting dimeric coiled-coil modules for functionalization of designed protein origami structures Vrije Universiteit Brussel

Andrea Majerle, San Hadzi, Jana Aupič, Tadej Satler, Fabio Lapenta, Žiga Strmšek, Jurij Lah, Remy Loris, Roman Jerala
Coiled-coils (CC) are widely used in protein design since their sequence-structure relationship is quite well-understood. In the CC protein origami (CCPO) approach a polypeptide chain is composed from a defined sequence of orthogonal CC building segments which fold into different polyhedral shapes such as tetrahedron, triangular prism, and four-sided pyramid. While noninteracting residues of the CCs can be engineered, additional ...

Arabidopsis Casein Kinase 2 triggers stem cell exhaustion under Al toxicity and phosphate deficiency through activation of the DNA damage response pathway Vrije Universiteit Brussel

Pengliang Wei, Manon Demulder, Pascale David, Thomas Eekhout, Kaoru O. Yoshiyama, Long Nguyen, Ilse Vercauteren, Dominique Eeckhout, Margot Galle, Paul Larsen, et al.
Aluminum (Al) toxicity and inorganic phosphate (Pi) limitation are widespread chronic abiotic and mutually enhancing stresses that profoundly affect crop yield. Both stresses cause a strong inhibition of root growth, resulting from a progressive exhaustion of the stem cell niche. Here, we report on a casein kinase 2 (CK2) inhibitor identified by its capability to maintain a functional root stem cell niche under Al toxic conditions. CK2 operates ...

Structure and substrate specificity determinants of the taurine biosynthetic enzyme cysteine sulphinic acid decarboxylase Vrije Universiteit Brussel

Elaheh Mahootchi, Arne Raasakka, Weisha Luan, Gopinath Muruganandam, Remy Loris, Jan Haavik, Petri Kursula

Pyridoxal 5́-phosphate (PLP) is an important cofactor for amino acid decarboxylases with many biological functions, including the synthesis of signalling molecules, such as serotonin, dopamine, histamine, γ-aminobutyric acid, and taurine. Taurine is an abundant amino acid with multiple physiological functions, including osmoregulation, pH regulation, antioxidative protection, and neuromodulation. In mammalian tissues, taurine is mainly ...

Molecular architecture of the endocytic TPLATE complex Vrije Universiteit Brussel Ghent University

Klaas Yperman, Jie Wang, Dominique Eeckhout, Joanna Winkler, Lam Dai Vu, Michael Vandorpe, Peter Grones, Evelien Mylle, Michael Kraus, Romain Merceron, et al.
Eukaryotic cells rely on endocytosis to regulate their plasma membrane proteome and lipidome. Most eukaryotic groups, except fungi and animals, have retained the evolutionary ancient TSET complex as endocytic regulator. Unlike other coatomer complexes, structural insight into TSET is lacking. Here, we reveal the molecular architecture of plant TSET (TPLATE complex/TPC) using an integrative structural approach. We identify crucial roles for ...