ReviewCurrent opinion in structural biology2016
The disordered hypervariable region and the folded catalytic domain of oncogenic K-Ras4B partner in phospholipid binding.
Review in Current opinion in structural biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 43 citations in OpenAlex.
- Pioneer in Molecular Biology: Conformational Ensembles in Molecular Recognition, Allostery, and Cell Function.Journal of molecular biology · 2025Review
- Review
- Recapitulation of cell-like KRAS4b membrane dynamics on complex biomimetic membranes.iScience · 2022Article
- Ras isoform-specific expression, chromatin accessibility, and signaling.Biophysical reviews · 2021Review
- Unveiling the Dynamics of KRAS4b on Lipid Model Membranes.The Journal of membrane biology · 2021Article
- Multivalent assembly of KRAS with the RAS-binding and cysteine-rich domains of CRAF on the membrane.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- A Non-Canonical Calmodulin Target Motif Comprising a Polybasic Region and Lipidated Terminal Residue Regulates Localization.International journal of molecular sciences · 2020Review
- The quaternary assembly of KRas4B with Raf-1 at the membrane.Computational and structural biotechnology journal · 2020Article
- Novel compound cedrelone inhibits hepatocellular carcinoma progression via PBLD and Ras/Rap1.Experimental and therapeutic medicine · 2019Article
- The Hypervariable Region of K-Ras4B Governs Molecular Recognition and Function.International journal of molecular sciences · 2019Review
- The structural basis for Ras activation of PI3Kα lipid kinase.Physical chemistry chemical physics : PCCP · 2019Article
- K-Ras G-domain binding with signaling lipid phosphatidylinositol (4,5)-phosphate (PIP2): membrane association, protein orientation, and function.The Journal of biological chemistry · 2019Article
- Review: Precision medicine and driver mutations: Computational methods, functional assays and conformational principles for interpreting cancer drivers.PLoS computational biology · 2019Review
- Calmodulin (CaM) Activates PI3Kα by Targeting the "Soft" CaM-Binding Motifs in Both the nSH2 and cSH2 Domains of p85α.The journal of physical chemistry. B · 2018Article
- Autoinhibition in Ras effectors Raf, PI3Kα, and RASSF5: a comprehensive review underscoring the challenges in pharmacological intervention.Biophysical reviews · 2018Review
- Cyclase-associated protein 1 (CAP1) is a prenyl-binding partner of Rap1 GTPase.The Journal of biological chemistry · 2018Article
- Raf-1 Cysteine-Rich Domain Increases the Affinity of K-Ras/Raf at the Membrane, Promoting MAPK Signaling.Structure (London, England : 1993) · 2018Article
- Oncogenic Ras Isoforms Signaling Specificity at the Membrane.Cancer research · 2018Review
- Phosphorylated Calmodulin Promotes PI3K Activation by Binding to the SHBiophysical journal · 2017Article
- Molecular Dynamics Simulations and Dynamic Network Analysis Reveal the Allosteric Unbinding of Monobody to H-Ras Triggered by R135K Mutation.International journal of molecular sciences · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The C-terminal hypervariable region (HVR) of the splice variant KRAS4B is disordered. Classically, the role of the post-translationally-modified HVR is to navigate Ras in the cell and to anchor it in localized plasma membrane regions. Here, we propose additional regulatory roles, including auto-inhibition by shielding the effector binding site in the GDP-bound state and release upon GTP binding and in the presence of certain oncogenic mutations. The released HVR can interact with calmodulin. We show that oncogenic mutations (G12V/G12D) modulate the HVR-phospholipid binding specificity, resulting in preferential interactions with phosphatidic acid. The shifts in the conformational preferences and binding specificity in the disordered state exemplify the critical role of the unstructured tail of K-Ras4B in cancer.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.