ArticleProceedings of the National Academy of Sciences of the United States of America2006
Structure-function-folding relationship in a WW domain.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 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
104 citing papers in PubMed, 220 citations in OpenAlex.
- Backbone double-mutant cycle analysis quantifies hydrogen-bond energies in proteins.Protein science : a publication of the Protein Society · 2026Article
- Optimized protein-water interactions and torsional refinements yield balanced atomistic protein force fields.Nature communications · 2025Article
- Pathway regulation mechanism by cotranslational protein folding.Communications chemistry · 2025Article
- Design and evolution of a synthetic small protein scaffold based on the WW domain.Protein science : a publication of the Protein Society · 2025Article
- Structural and energetic analysis of stabilizing indel mutations.bioRxiv : the preprint server for biology · 2024Article
- Spectral Map for Slow Collective Variables, Markovian Dynamics, and Transition State Ensembles.Journal of chemical theory and computation · 2024Article
- Conservation of kinetic stability, but not the unfolding mechanism, between human transthyretin and a transthyretin-related enzyme.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Uncertainties in Markov State Models of Small Proteins.Journal of chemical theory and computation · 2023Article
- Regulation of eukaryotic protein kinases by Pin1, a peptidyl-prolyl isomerase.Advances in biological regulation · 2023Article
- Identification of novel functional mini-receptors by combinatorial screening of split-WW domains.Chemical science · 2022Article
- Proton TOCSY NMR relaxation rates quantitate protein side chain mobility in the Pin1 WW domain.Journal of biomolecular NMR · 2022Article
- The CSY-protecting group in the microwave-assisted synthesis of aggregation-prone peptides.RSC chemical biology · 2022Article
- Folding in Place: Design of β-Strap Motifs to Stabilize the Folding of Hairpins with Long Loops.The Journal of organic chemistry · 2021Article
- Time-Lagged Independent Component Analysis of Random Walks and Protein Dynamics.Journal of chemical theory and computation · 2021Article
- Sampling of the conformational landscape of small proteins with Monte Carlo methods.Scientific reports · 2020Article
- Simple Model of Protein Energetics To Identify Ab Initio Folding Transitions from All-Atom MD Simulations of Proteins.Journal of chemical theory and computation · 2020Article
- Increasing protein stability by engineering the n → π* interaction at the β-turn.Chemical science · 2020Article
- New Insights into Folding, Misfolding, and Nonfolding Dynamics of a WW Domain.The journal of physical chemistry. B · 2020Article
- Adaptive Markov state model estimation using short reseeding trajectories.The Journal of chemical physics · 2020Article
- Activity and Affinity of Pin1 Variants.Molecules (Basel, Switzerland) · 2019Review
44 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Protein folding barriers result from a combination of factors including unavoidable energetic frustration from nonnative interactions, natural variation and selection of the amino acid sequence for function, and/or selection pressure against aggregation. The rate-limiting step for human Pin1 WW domain folding is the formation of the loop 1 substructure. The native conformation of this six-residue loop positions side chains that are important for mediating protein-protein interactions through the binding of Pro-rich sequences. Replacement of the wild-type loop 1 primary structure by shorter sequences with a high propensity to fold into a type-I' beta-turn conformation or the statistically preferred type-I G1 bulge conformation accelerates WW domain folding by almost an order of magnitude and increases thermodynamic stability. However, loop engineering to optimize folding energetics has a significant downside: it effectively eliminates WW domain function according to ligand-binding studies. The energetic contribution of loop 1 to ligand binding appears to have evolved at the expense of fast folding and additional protein stability. Thus, the two-state barrier exhibited by the wild-type human Pin1 WW domain principally results from functional requirements, rather than from physical constraints inherent to even the most efficient loop formation process.
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.