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Record W4407074312 · doi:10.1021/jacs.4c13008

Intermolecular Misfolding Captured in Parallelly Organized Titin

2025· article· en· W4407074312 on OpenAlexafffund
Hongbin Li

Bibliographic record

VenueJournal of the American Chemical Society · 2025
Typearticle
Languageen
FieldPhysics and Astronomy
TopicForce Microscopy Techniques and Applications
Canadian institutionsUniversity of British Columbia
FundersNatural Sciences and Engineering Research Council of CanadaHeart and Stroke Foundation of Canada
KeywordsChemistryTitinIntermolecular forceBiophysicsNanotechnologyMoleculeCell biologyOrganic chemistrySarcomere

Abstract

fetched live from OpenAlex

The giant muscle protein titin is largely responsible for the passive elasticity of the muscles. The I-band part of titin is elastic, and its constitutive immunoglobulin (Ig) domains undergo force-induced unfolding and refolding when the muscle is stretched toward or beyond the end of the physiological range of sarcomere length. Correct folding of the titin Ig domains is essential to the structure and functions of titin. Although our knowledge of titin elasticity at the molecular level has been largely obtained from single molecule experiments, titin does not exist as an isolated molecule. Instead, six titins are parallelly organized in the muscle sarcomeres. It remains unknown what impact such a parallel organization brings on the folding of titin Ig domains and titin elasticity. Using the two-molecule force spectroscopy technique, here, we report the direct observation of the intermolecular misfolding of titin Ig domains that are arranged in parallel. Our results reveal that when parallelly arranged, two I94 domains can misfold into an intermolecular domain-swapped state that is thermally and mechanically stable. Such intermolecular misfolding may play important structural and functional roles in titin organization and elasticity.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.009
Threshold uncertainty score0.228

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.003
GPT teacher head0.263
Teacher spread0.259 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations4
Published2025
Admission routes2
Has abstractyes

Explore more

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