Comprehensive Collection and Prediction of ABC Transmembrane Protein Structures in the AI Era of Structural Biology

Tordai, Hedvig; Suhajda, Erzsebet; Sillitoe, Ian; Nair, Sreenath; Váradi, Mihály; Hegedüs, Tamás

doi:10.3390/ijms23168877

Cited by 14 publications

(16 citation statements)

References 76 publications

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“…Since the number of known protein complexes is immense, having a comprehensive database for complex structures soon is rather unlikely. Therefore, integrating 3D data from experts in specialised fields of proteins is important, as demonstrated by physiologically and pathologically relevant transmembrane ABC half transporters 26 and by a set of computed structures of core eukaryotic protein complexes deposited in the ModelArchive 27 . Databases such as the Small-Angle Scattering Biological Data Bank (SASBDB) 28 and the Protein Ensemble Database (PED) 22 highlight the dynamic nature of intrinsically disordered proteins (Figure 2B).…”

Section: Figure 1 -Growth Of the Uniprot And The Pdb Databasesmentioning

confidence: 99%

3D-Beacons: Decreasing the gap between protein sequences and structures through a federated network of protein structure data resources

Váradi

Nair

Sillitoe

et al. 2022

Preprint

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While scientists can often infer the biological function of proteins from their 3-dimensional quaternary structures, the gap between known protein sequences and their experimentally determined structures keeps increasing. A potential solution to this problem is presented by ever more sophisticated theoretical protein modelling approaches. While often powerful on their own, most methods have strengths and weaknesses. Therefore, it benefits researchers to examine models from various data providers and perform comparative analysis to identify what models best address their specific use cases. To make data from a large array of model providers more easily accessible to the broader scientific community, we established 3D-Beacons, a collaborative initiative to create a federated network with unified data access mechanisms. 3D-Beacons allows researchers to collate coordinate files and metadata for experimentally determined and theoretical protein models from state-of-the-art and specialist model providers and the Protein Data Bank.

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Section: Figure 1 -Growth Of the Uniprot And The Pdb Databasesmentioning

confidence: 99%

3D-Beacons: Decreasing the gap between protein sequences and structures through a federated network of protein structure data resources

Váradi

Nair

Sillitoe

et al. 2022

Preprint

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“…The CLs drive TMD1/2 conformational transitions upon NBD association-dissociation cycles. The NBD/TMD coupling is a requirement for substrate translocation and is facilitated by domainswapped structural elements in Pgp-like (Type IV) exporters, which enable communication of each domain with all the others [1][2][3] .…”

Section: Introductionmentioning

confidence: 99%

Folding correctors can restore CFTR posttranslational folding landscape by allosteric domain-domain coupling

Soya,

Xu,

Roldan

et al. 2023

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The folding/misfolding and pharmacological rescue of multidomain ATP-binding cassette (ABC) C-subfamily transporters, essential for organismal health, remain incompletely understood. The ABCC transporters core consists of two nucleotide binding domains (NBD1,2) and transmembrane domains (TMD1,2). Using molecular dynamic simulations, biochemical and hydrogen deuterium exchange approaches, we show that the mutational uncoupling or stabilization of NBD1-TMD1/2 interfaces can compromise or facilitate the CFTR(ABCC7)-, MRP1(ABCC1)-, and ABCC6-transporters posttranslational coupled domain-folding in the endoplasmic reticulum. Allosteric or orthosteric binding of VX-809 and/or VX-445 folding correctors to TMD1/2 can rescue kinetically trapped CFTR post-translational folding intermediates of cystic fibrosis (CF) mutants of NBD1 or TMD1 by global rewiring inter-domain allosteric-networks. We propose that dynamic allosteric domain-domain communications not only regulate ABCC-transporters function but are indispensable to tune the folding landscape of their post-translational intermediates. These allosteric networks can be compromised by CF-mutations, and reinstated by correctors, offering a framework for mechanistic understanding of ABCC-transporters (mis)folding.

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“…Since the number of known protein complexes is immense, having a comprehensive database for complex structures soon is rather unlikely. Therefore, integrating 3-dimensional data from experts in specialized fields of proteins is important, as demonstrated by physiologically and pathologically relevant transmembrane ABC half transporters [ 26 ] and by a set of computed structures of core eukaryotic protein complexes deposited in the ModelArchive [ 27 ]. Databases such as the Small-Angle Scattering Biological Data Bank (SASBDB) [ 28 ] and the Protein Ensemble Database (PED) [ 22 ] highlight the dynamic nature of intrinsically disordered proteins (Fig.…”

Section: Introductionmentioning

confidence: 99%

3D-Beacons: decreasing the gap between protein sequences and structures through a federated network of protein structure data resources

et al. 2022

Self Cite

View full text Add to dashboard Cite

While scientists can often infer the biological function of proteins from their 3-dimensional quaternary structures, the gap between the number of known protein sequences and their experimentally determined structures keeps increasing. A potential solution to this problem is presented by ever more sophisticated computational protein modeling approaches. While often powerful on their own, most methods have strengths and weaknesses. Therefore, it benefits researchers to examine models from various model providers and perform comparative analysis to identify what models can best address their specific use cases. To make data from a large array of model providers more easily accessible to the broader scientific community, we established 3D-Beacons, a collaborative initiative to create a federated network with unified data access mechanisms. The 3D-Beacons Network allows researchers to collate coordinate files and metadata for experimentally determined and theoretical protein models from state-of-the-art and specialist model providers and also from the Protein Data Bank.

show abstract

Comprehensive Collection and Prediction of ABC Transmembrane Protein Structures in the AI Era of Structural Biology

Cited by 14 publications

References 76 publications

3D-Beacons: Decreasing the gap between protein sequences and structures through a federated network of protein structure data resources

3D-Beacons: Decreasing the gap between protein sequences and structures through a federated network of protein structure data resources

Folding correctors can restore CFTR posttranslational folding landscape by allosteric domain-domain coupling

3D-Beacons: decreasing the gap between protein sequences and structures through a federated network of protein structure data resources

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