ArticlePloS one2014
Transmembrane recognition of the semaphorin co-receptors neuropilin 1 and plexin A1: coarse-grained simulations.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- PlexinA1 (PLXNA1) as a novel scaffold protein for the engineering of extracellular vesicles.Journal of extracellular vesicles · 2024Article
- Plexin-B1 and Plexin-B2 play non-redundant roles in GABAergic synapse formation.Molecular and cellular neurosciences · 2024Article
- Heightened cocaine-seeking in male rats associates with a distinct transcriptomic profile in the medial prefrontal cortex.Frontiers in pharmacology · 2022Article
- Membrane receptor activation mechanisms and transmembrane peptide tools to elucidate them.The Journal of biological chemistry · 2020Review
- Computational Modeling of Realistic Cell Membranes.Chemical reviews · 2019Review
- Neuropilins in the Context of Tumor Vasculature.International journal of molecular sciences · 2019Review
- Current drug design to target the Semaphorin/Neuropilin/Plexin complexes.Cell adhesion & migration · 2016Review
- Inhibition of PlexA1-mediated brain tumor growth and tumor-associated angiogenesis using a transmembrane domain targeting peptide.Oncotarget · 2016Article
- Inhibition of primary breast tumor growth and metastasis using a neuropilin-1 transmembrane domain interfering peptide.Oncotarget · 2016Article
- Association of Peripheral Membrane Proteins with Membranes: Free Energy of Binding of GRP1 PH Domain with Phosphatidylinositol Phosphate-Containing Model Bilayers.The journal of physical chemistry letters · 2016Article
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- A cytosolic juxtamembrane interface modulates plexin A3 oligomerization and signal transduction.PloS one · 2015Article
- The X-ray structure of NccX from Cupriavidus metallidurans 31A illustrates potential dangers of detergent solubilization when generating and interpreting crystal structures of membrane proteins.The Journal of biological chemistry · 2014Article
- Dimerization of the EphA1 receptor tyrosine kinase transmembrane domain: Insights into the mechanism of receptor activation.Biochemistry · 2014Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cancer associated class 3 semaphorins require direct binding to neuropilins and association to plexins to trigger cell signaling. Here, we address the role of the transmembrane domains of neuropilin 1 and plexin A1 for the dimerization of the two receptors by characterizing the assembly in lipid bilayers using coarse-grained molecular dynamics simulations. From experimental evidence using a two-hybrid system showing the biochemical association of the two receptors transmembrane domains, we performed molecular simulations in DOPC and POPC demonstrating spontaneously assembly to form homodimers and heterodimers with a very high propensity for right-handed packing of the helices. Inversely, left-handed packing was observed with a very low propensity. This mode of packing was observed uniquely when the plexin A1 transmembrane domain was involved in association. Potential of mean force calculations were used to predict a hierarchy of self-association for the monomers: the two neuropilin 1 transmembrane domains strongly associated, neuropilin 1 and plexin A1 transmembrane domains associated less and the two plexin A1 transmembrane domains weakly but significantly associated. We demonstrated that homodimerization and heterodimerization are driven by GxxxG motifs, and that the sequence context modulates the packing mode of the plexin A1 transmembrane domains. This work presents major advances towards our understanding of membrane signaling platforms assembly through membrane domains and provides exquisite information for the design of antagonist drugs defining a novel class of therapeutic agents.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.