3DSwap: curated knowledgebase of proteins involved in 3D domain swapping

Shameer, Khader; Shingate, Prashant; Manjunath, S. C. P.; Karthika, M.; Pugalenthi, Ganesan; Sowdhamini, Ramanathan

doi:10.1093/database/bar042

Cited by 28 publications

(30 citation statements)

References 112 publications

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“…The structures and the sequences of hinge loops have been extensively studied in order to understand their role in domain-swapping. [50][51] In stefin-B, loop1 is a turn in the monomer (Fig. 1A) and transforms into a β-strand in the dimer (Fig.…”

Section: Resultsmentioning

confidence: 99%

Protein Domain-Swapping Can Be a Consequence of Functional Residues

Mascarenhas

Gosavi

2016

J. Phys. Chem. B

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Monomer topology has been implicated in domain-swapping, a potential first step on the route to disease-causing protein aggregation. Despite having the same topology (β1-α1-β2-β3-β4-β5), the cysteine protease inhibitor stefin-B domain swaps more readily than a single-chain variant of the heterodimeric sweet protein monellin (scMn). Here, we computationally study the folding of stefin-B and scMn in order to understand the molecular basis for the difference in their domain-swapping propensities. In agreement with experiments, our structure-based simulations show that scMn folds cooperatively without the population of an intermediate while stefin-B populates an equilibrium intermediate state. Since the simulation intermediate has only one domain structured (β3-β4-β5), it can directly lead to domain-swapping. Using computational variants of stefin-B, we show that the population of this intermediate is caused by regions of stefin-B that have been implicated in protease inhibition. We also find that the protease-binding regions are located on two structural elements and localized in space. In contrast, the residues that contribute to the sweetness of monellin are not localized to a few structural elements but are distributed over the protein fold. We conclude that the distributed functional residues of monellin do not induce large local perturbations in the protein structure, eliminating the formation of folding intermediates and in turn domain-swapping. On the other hand, the localized protease-binding regions of stefin-B promote the formation of a folding intermediate which can lead to domain-swapping. Thus, domain-swapping can be a direct consequence of the constraints that function imposes on the protein structure.

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Section: Resultsmentioning

confidence: 99%

Protein Domain-Swapping Can Be a Consequence of Functional Residues

Mascarenhas

Gosavi

2016

J. Phys. Chem. B

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“…This corresponds to an 83% extent of swapping as defined in the domain swapping 3D knowledge database (http://caps.ncbs.res.in/3dswap/index.html). (Shameer et al, 2011) The two domains in the dimer are each highly similar to that of the monomer hCRBPII structure with RMSD ranging from 0.382–0.397 between monomeric hCRBPII and a single domain of the dimer (Figures 1D and S1D). The four domain swapped dimer structures so far determined have in common a large rotation about the psi angle of Thr 56.…”

Section: Resultsmentioning

confidence: 81%

Domain-Swapped Dimers of Intracellular Lipid-Binding Proteins: Evidence for Ordered Folding Intermediates

et al. 2016

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Human Cellular Retinol Binding Protein II (hCRBPII), a member of the intracellular Lipid binding protein family, is a monomeric protein responsible for the intracellular transport of retinol and retinal. Herein we report that hCRBPII forms an extensive domain swapped dimer during bacterial expression. The domain swapped region encompasses almost half of the protein. The dimer represents a novel structural architecture with the mouths of the two binding cavities facing each other, producing a new binding cavity that spans the length of the protein complex. Though wild-type hCRBPII forms the dimer, the propensity for dimerization can be substantially increased via mutation at Tyr60. The monomeric form of the wild type protein represents the thermodynamically more stable species, making the domain swapped dimer a kinetically trapped entity. Hypothetically, the wild type protein has evolved to minimize dimerization of the folding intermediate through a critical hydrogen bond (Tyr60-Glu72) that disfavors the dimeric form.

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“…Specialized molecular-class-specific databases that catalog a group of proteins related to molecular mechanisms or disease types are also available. For example, proteins associated with 3D domain swapping, a key molecular basis for neurodegenerative diseases, is compiled in the 3DSwap knowledgebase [52]. Such efforts are underway to compile and provide health care data in the public domain.…”

Section: Aggregation Of Real-time Biomedical and Health Care Datamentioning

confidence: 99%

Translational bioinformatics in the era of real-time biomedical, health care and wellness data streams

Shameer¹,

et al. 2016

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Monitoring and modeling biomedical, health care and wellness data from individuals and converging data on a population scale have tremendous potential to improve understanding of the transition to the healthy state of human physiology to disease setting. Wellness monitoring devices and companion software applications capable of generating alerts and sharing data with health care providers or social networks are now available. The accessibility and clinical utility of such data for disease or wellness research are currently limited. Designing methods for streaming data capture, real-time data aggregation, machine learning, predictive analytics and visualization solutions to integrate wellness or health monitoring data elements with the electronic medical records (EMRs) maintained by health care providers permits better utilization. Integration of population-scale biomedical, health care and wellness data would help to stratify patients for active health management and to understand clinically asymptomatic patients and underlying illness trajectories. In this article, we discuss various health-monitoring devices, their ability to capture the unique state of health represented in a patient and their application in individualized diagnostics, prognosis, clinical or wellness intervention. We also discuss examples of translational bioinformatics approaches to integrating patient-generated data with existing EMRs, personal health records, patient portals and clinical data repositories. Briefly, translational bioinformatics methods, tools and resources are at the center of these advances in implementing real-time biomedical and health care analytics in the clinical setting. Furthermore, these advances are poised to play a significant role in clinical decision-making and implementation of data-driven medicine and wellness care.

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3DSwap: curated knowledgebase of proteins involved in 3D domain swapping

Cited by 28 publications

References 112 publications

Protein Domain-Swapping Can Be a Consequence of Functional Residues

Protein Domain-Swapping Can Be a Consequence of Functional Residues

Domain-Swapped Dimers of Intracellular Lipid-Binding Proteins: Evidence for Ordered Folding Intermediates

Translational bioinformatics in the era of real-time biomedical, health care and wellness data streams

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