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Record W3027479247 · doi:10.1101/2020.05.18.099887

Novel insights into the structure and transport mechanisms of TAPT1

2020· preprint· en· W3027479247 on OpenAlexafffund
Md Sorwer Alam Parvez, Mohammad Mahfujur Rahman, Md. Niaz Morshed, Dolilur Rahman, Saeed Anwar, Paul Coucke, Mohammad Jakir Hosen

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2020
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic and Kidney Cyst Diseases
Canadian institutionsUniversity of Alberta
FundersAlberta InnovatesShahjalal University of Science and Technology
KeywordsCiliumIn silicoCiliopathiesTransmembrane proteinTransmembrane domainBiophysicsComputational biologyProtein structureMutantBiologyChemistryGeneCell biologyCrystallographyGeneticsBiochemistryPhenotype

Abstract

fetched live from OpenAlex

Abstract Transmembrane anterior-posterior transformation protein 1 (TAPT1), encoded by the TAPT1 gene expressed in the basal ciliary body, plays a crucial role in cilia formation as well as axial skeletal patterning. Mutations in this gene have been reported to cause several ciliopathies and osteo-related diseases. Unfortunately, the cellular and molecular pathogenic mechanisms are still unclear also due to the lack of X-ray crystallographic structure and further characterization of TAPT1 protein. In this study, we attempted to characterize this protein by in silico techniques. A 3D structure of TAPT1 was generated by the ab initio method, which was further used for the analysis of the substrate-binding site, to determine pore size and for the prediction of the possible substrate(s). Validation by using different software packages revealed a reliable 3D model of TAPT1. Topology modeling revealed that TAPT1 has eight transmembrane helices with a total number of 27 helices in secondary structure. The amino acid residues H235, R323, K443, N446, S447, L450, K453, S454, Y457, K511, N513, D533, K535, D536, and T538 were found to form the pore surface as well as involved in the binding interaction with the substrate(s). This study predicted flavonoids as the possible substrate for TAPT1, which could further be confirmed by ingenuity pathway analysis. Moreover, our analysis indicated that TAPT1 might localize in the mitochondrial membrane in addition to the ciliary basal body. Our study gives novel insights for TAPT1 structure and its function.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

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 communication0.0000.001
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.007
GPT teacher head0.197
Teacher spread0.189 · 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 source (direct Gemma or distilled Codex), 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

Citations2
Published2020
Admission routes2
Has abstractyes

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