ArticleNature communications2015
Transient misfolding dominates multidomain protein folding.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 124 citations in OpenAlex.
- Differential proteostatic regulation of insoluble and abundant proteins.Bioinformatics (Oxford, England) · 2019Pooled it
- Residue-Level Energetic Analysis of Transient Misfolding in the Whirlin PDZ Tandem Reveals a Possible Connection to an AlphaFold-Predicted Alternative Topology.International journal of molecular sciences · 2026Article
- Dimerization of natively folded molecules drives misfolding and aggregation in Cys-depleted variants of cataract-associated human lens γD-crystallin.The Journal of biological chemistry · 2026Article
- Dimerization of natively folded molecules drives misfolding and aggregation in Cys-depleted variants of cataract-associated human lens γD-crystallin.bioRxiv : the preprint server for biology · 2026Article
- Determinants of Protein Folding Pathways: Lessons from Metamorphic Proteins.International journal of molecular sciences · 2026Review
- Dissecting the Structural Features of Folding Asymmetry and Transient Misfolding in a Multidomain PDZ Scaffold.Small science · 2026Article
- Adjacent domains drive the emergence of misfolded intermediates in the folding pathway of the PDZ4 from MAGI1.BBA advances · 2026Article
- Force writes memory: proline isomerization as a molecular memory switch.Biochemical Society transactions · 2025Review
- The human ribosome modulates multidomain protein biogenesis by delaying cotranslational domain docking.Nature structural & molecular biology · 2025Article
- Formation of an Amyloid-like Structure During In Vitro Interaction of Titin and Myosin-Binding Protein C.International journal of molecular sciences · 2025Article
- A PDZ tandem repeat folds and unfolds via different pathways.Protein science : a publication of the Protein Society · 2024Article
- GRB2: A dynamic adaptor protein orchestrating cellular signaling in health and disease.Biochemistry and biophysics reports · 2024Review
- Investigation of Structural Peculiarities of Smooth Muscle Titin Aggregates, Formed under Different In Vitro Conditions, by Small-Angle X-Ray Scattering and Fourier Transform Infrared Spectroscopy.Bulletin of experimental biology and medicine · 2024Article
- Proactive vaccination using multiviral Quartet Nanocages to elicit broad anti-coronavirus responses.Nature nanotechnology · 2024Article
- Folding and Binding Kinetics of the Tandem of SH2 Domains from SHP2.International journal of molecular sciences · 2024Article
- N-glycosylation as a eukaryotic protective mechanism against protein aggregation.Science advances · 2024Article
- Mechanisms and pathology of protein misfolding and aggregation.Nature reviews. Molecular cell biology · 2023Review
- Systematic conformation-to-phenotype mapping via limited deep sequencing of proteins.Molecular cell · 2023Article
- Article
- Nonspecific Amyloid Aggregation of Chicken Smooth-Muscle Titin: In Vitro Investigations.International journal of molecular sciences · 2023Article
2 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
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Neighbouring domains of multidomain proteins with homologous tandem repeats have divergent sequences, probably as a result of evolutionary pressure to avoid misfolding and aggregation, particularly at the high cellular protein concentrations. Here we combine microfluidic-mixing single-molecule kinetics, ensemble experiments and molecular simulations to investigate how misfolding between the immunoglobulin-like domains of titin is prevented. Surprisingly, we find that during refolding of tandem repeats, independent of sequence identity, more than half of all molecules transiently form a wide range of misfolded conformations. Simulations suggest that a large fraction of these misfolds resemble an intramolecular amyloid-like state reported in computational studies. However, for naturally occurring neighbours with low sequence identity, these transient misfolds disappear much more rapidly than for identical neighbours. We thus propose that evolutionary sequence divergence between domains is required to suppress the population of long-lived, potentially harmful misfolded states, whereas large populations of transient misfolded states appear to be tolerated.
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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.