Salamina, Marco Montefiore, Bailey C Liu, Mengxi Wood, Daniel J Heath, Richard Ault, James R Wang, Lan-Zhen Korolchuk, Svitlana Baslé, Arnaud Pastok, Martyna W
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Published in
Journal of molecular biology
The SCFSKP2 ubiquitin ligase relieves G1 checkpoint control of CDK-cyclin complexes by promoting p27KIP1 degradation. We describe reconstitution of stable complexes containing SKP1-SKP2 and CDK1-cyclin B or CDK2-cyclin A/E, mediated by the CDK regulatory subunit CKS1. We further show that a direct interaction between a SKP2 N-terminal motif and cyc...
Magnussen, Helge M. Huang, Danny T.
Published in
Journal of Molecular Biology
As a key regulator of the tumour suppressor protein p53, MDM2 is involved in various types of cancer and has thus been an attractive drug target. So far, small molecule design has primarily focussed on the N-terminal p53-binding domain although on-target toxicity effects have been reported. Targeting the catalytic RING domain of MDM2 resembles an a...
Allen, Joel D Watanabe, Yasunori Chawla, Himanshi Newby, Maddy L Crispin, Max
Published in
Journal of molecular biology
The severity of SARS-CoV-2 infection is highly variable and yet the molecular basis for this effect remains elusive. One potential contribution are differences in the glycosylation of target human cells, particularly as SARS-CoV-2 has the capacity to bind sialic acid which is a common, and highly variable, terminal modification of glycans. The vira...
Tugaeva, Kristina V. Hawkins, Dorothy E.D.P. Smith, Jake L.R. Bayfield, Oliver W. Ker, De-Sheng Sysoev, Andrey A. Klychnikov, Oleg I. Antson, Alfred A. Sluchanko, Nikolai N.
Published in
Journal of Molecular Biology
The coronavirus nucleocapsid protein (N) controls viral genome packaging and contains numerous phosphorylation sites located within unstructured regions. Binding of phosphorylated SARS-CoV N to the host 14-3-3 protein in the cytoplasm was reported to regulate nucleocytoplasmic N shuttling. All seven isoforms of the human 14-3-3 are abundantly prese...
Ramlaul, Kailash Fu, Wencheng Li, Hua de Martin Garrido, Natàlia He, Lin Trivedi, Manjari Cui, Wei Aylett, Christopher H.S. Wu, Geng
Published in
Journal of Molecular Biology
The Tuberous Sclerosis Complex (TSC) protein complex (TSCC), comprising TSC1, TSC2, and TBC1D7, is widely recognised as a key integration hub for cell growth and intracellular stress signals upstream of the mammalian target of rapamycin complex 1 (mTORC1). The TSCC negatively regulates mTORC1 by acting as a GTPase-activating protein (GAP) towards t...
Hattori, Takamitsu Koide, Akiko Noval, Maria G. Panchenko, Tatyana Romero, Larizbeth A. Teng, Kai Wen Tada, Takuya Landau, Nathaniel R. Stapleford, Kenneth A. Koide, Shohei
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Published in
Journal of Molecular Biology
The COVID-19 pandemic remains a global threat, and host immunity remains the main mechanism of protection against the disease. The spike protein on the surface of SARS-CoV-2 is a major antigen and its engagement with human ACE2 receptor plays an essential role in viral entry into host cells. Consequently, antibodies targeting the ACE2-interacting s...
Verzini, Silvia Shah, Maliha Theillet, Francois-Xavier Belsom, Adam Bieschke, Jan Wanker, Erich E. Rappsilber, Juri Binolfi, Andres Selenko, Philipp
Published in
Journal of Molecular Biology
Heterogeneous aggregates of the human protein α-synuclein (αSyn) are abundantly found in Lewy body inclusions of Parkinson’s disease patients. While structural information on classical αSyn amyloid fibrils is available, little is known about the conformational properties of disease-relevant, non-canonical aggregates. Here, we analyze the structural...
Arya, Rimanshee Kumari, Shweta Pandey, Bharati Mistry, Hiral Bihani, Subhash C Das, Amit Prashar, Vishal Gupta, Gagan D Panicker, Lata Kumar, Mukesh
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Published in
Journal of molecular biology
The unprecedented scale of the ongoing COVID-19 pandemic has catalyzed an intense effort of the global scientific community to unravel different aspects of the disease in a short time. One of the crucial aspects of these developments is the determination of more than three hundred experimental structures of SARS-CoV-2 proteins in the last few month...
Fineberg, Adam Surrey, Thomas Kukura, Philipp
Published in
Journal of Molecular Biology
The α β -tubulin heterodimer is the fundamental building block of microtubules, making it central to several cellular processes. Despite the apparent simplicity of heterodimerisation, the associated energetics and kinetics remain disputed, largely due to experimental challenges associated with quantifying affinities in the 10−2 s−1. Our results dem...
Tomkuvienė, Miglė Ikasalaitė, Diana Slyvka, Anton Rukšėnaitė, Audronė Ravichandran, Mirunalini Jurkowski, Tomasz P. Bochtler, Matthias Klimašauskas, Saulius
Published in
Journal of Molecular Biology
Methylation of cytosine to 5-methylcytosine (mC) is a prevalent reversible epigenetic mark in vertebrates established by DNA methyltransferases (MTases); the methylation mark can be actively erased via a multi-step demethylation mechanism involving oxidation by Ten-eleven translocation (TET) enzyme family dioxygenases, excision of the latter oxidat...
