ArticleProceedings of the National Academy of Sciences of the United States of America2011
Malleability of folding intermediates in the homeodomain superfamily.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 22 citations in OpenAlex.
- Singular value decomposition of protein sequences as a method to visualize sequence and residue space.Protein science : a publication of the Protein Society · 2022Article
- Oncogenic Mutations in the DNA-Binding Domain of FOXO1 that Disrupt Folding: Quantitative Insights from Experiments and Molecular Simulations.Biochemistry · 2022Article
- High Energy Channeling and Malleable Transition States: Molecular Dynamics Simulations and Free Energy Landscapes for the Thermal Unfolding of Protein U1A and 13 Mutants.Biomolecules · 2022Article
- Complex Folding Landscape of Apomyoglobin at Acidic pH Revealed by Ultrafast Kinetic Analysis of Core Mutants.The journal of physical chemistry. B · 2018Article
- Characterization of protein folding by a Φ-value calculation with a statistical-mechanical model.Biophysics and physicobiology · 2016Article
- Fold and flexibility: what can proteins' mechanical properties tell us about their folding nucleus?Journal of the Royal Society, Interface · 2015Article
- Even with nonnative interactions, the updated folding transition states of the homologs Proteins G & L are extensive and similar.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Mechanistic studies of the biogenesis and folding of outer membrane proteins in vitro and in vivo: what have we learned to date?Archives of biochemistry and biophysics · 2014Review
- REMD and umbrella sampling simulations to probe the energy barrier of the folding pathways of engrailed homeodomain.Journal of molecular modeling · 2014Article
- Evidence for steric regulation of fibrinogen binding to Staphylococcus aureus fibronectin-binding protein A (FnBPA).The Journal of biological chemistry · 2014Article
- The folding of a family of three-helix bundle proteins: spectrin R15 has a robust folding nucleus, unlike its homologous neighbours.Journal of molecular biology · 2014Article
- Investigation of homeodomain membrane translocation properties: insights from the structure determination of engrailed-2 homeodomain in aqueous and membrane-mimetic environments.Biophysical journal · 2013Article
- Atomic-level description of ubiquitin folding.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Take home lessons from studies of related proteins.Current opinion in structural biology · 2013Review
- Conformational properties of the unfolded state of Im7 in nondenaturing conditions.Journal of molecular biology · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Members of the homeodomain superfamily are three-helix bundle proteins whose second and third helices form a helix-turn-helix motif (HTH). Their folding mechanism slides from the ultrafast, three-state framework mechanism for the engrailed homeodomain (EnHD), in which the HTH motif is independently stable, to an apparent two-state nucleation-condensation model for family members with an unstable HTH motif. The folding intermediate of EnHD has nearly native HTH structure, but it is not docked with helix1. The determinant of whether two- or three-state folding was hypothesized to be the stability of the HTH substructure. Here, we describe a detailed Φ-value analysis of the folding of the Pit1 homeodomain, which has similar ultrafast kinetics to that of EnHD. Formation of helix1 was strongly coupled with formation of HTH, which was initially surprising because they are uncoupled in the EnHD folding intermediate. However, we found a key difference between Pit1 and EnHD: The isolated peptide corresponding to the HTH motif in Pit1 was not folded in the absence of H1. Independent molecular dynamics simulations of Pit1 unfolding found an intermediate with H1 misfolded onto the HTH motif. The Pit1 folding pathway is the connection between that of EnHD and the slower folding homeodomains and provides a link in the transition of mechanisms from two- to three-state folding in this superfamily. The malleability of folding intermediates can lead to unstable substructures being stabilized by a variety of nonnative interactions, adding to the continuum of folding mechanisms.
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.