Dataset Information

Filling out the structural map of the NTF2-like superfamily.

ABSTRACT:

Background

The NTF2-like superfamily is a versatile group of protein domains sharing a common fold. The sequences of these domains are very diverse and they share no common sequence motif. These domains serve a range of different functions within the proteins in which they are found, including both catalytic and non-catalytic versions. Clues to the function of protein domains belonging to such a diverse superfamily can be gleaned from analysis of the proteins and organisms in which they are found.

Results

Here we describe three protein domains of unknown function found mainly in bacteria: DUF3828, DUF3887 and DUF4878. Structures of representatives of each of these domains: BT_3511 from Bacteroides thetaiotaomicron (strain VPI-5482) [PDB:3KZT], Cj0202c from Campylobacter jejuni subsp. jejuni serotype O:2 (strain NCTC 11168) [PDB:3K7C], rumgna_01855) and RUMGNA_01855 from Ruminococcus gnavus (strain ATCC 29149) [PDB:4HYZ] have been solved by X-ray crystallography. All three domains are similar in structure and all belong to the NTF2-like superfamily. Although the function of these domains remains unknown at present, our analysis enables us to present a hypothesis concerning their role.

Conclusions

Our analysis of these three protein domains suggests a potential non-catalytic ligand-binding role. This may regulate the activities of domains with which they are combined in the same polypeptide or via operonic linkages, such as signaling domains (e.g. serine/threonine protein kinase), peptidoglycan-processing hydrolases (e.g. NlpC/P60 peptidases) or nucleic acid binding domains (e.g. Zn-ribbons).

SUBMITTER: Eberhardt RY

PROVIDER: S-EPMC3924330 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Publications

Filling out the structural map of the NTF2-like superfamily.

Eberhardt Ruth Y RY Chang Yuanyuan Y Bateman Alex A Murzin Alexey G AG Axelrod Herbert L HL Hwang William C WC Aravind L L

BMC bioinformatics 20131119

<h4>Background</h4>The NTF2-like superfamily is a versatile group of protein domains sharing a common fold. The sequences of these domains are very diverse and they share no common sequence motif. These domains serve a range of different functions within the proteins in which they are found, including both catalytic and non-catalytic versions. Clues to the function of protein domains belonging to such a diverse superfamily can be gleaned from analysis of the proteins and organisms in which they ...[more]

PMID: 24246060

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Project description:ImportanceOne-third of US residents have trouble paying their medical bills. They often turn to their physicians for help navigating health costs and insurance coverage.ObjectiveTo determine whether physicians can accurately estimate out-of-pocket expenses when they are given all of the necessary information about a drug's price and a patient's insurance plan.Design, setting, and participantsThis national mail-in survey used a random sample of US physicians. The survey was sent to 900 outpatient physicians (300 each of primary care, gastroenterology, and rheumatology). Physicians were excluded if they were in training, worked primarily for the Veterans Administration or Indian Health Service, were retired, or reported 0% outpatient clinical effort. Analyses were performed from July to December 2020.Main outcomes and measuresIn a hypothetical vignette, a patient was prescribed a new drug costing $1000/month without insurance. A summary of her private insurance information was provided, including the plan's deductible, coinsurance rates, copays, and out-of-pocket maximum. Physicians were asked to estimate the drug's out-of-pocket cost at 4 time points between January and December, using the plan's 4 types of cost-sharing: (1) deductibles, (2) coinsurance, (3) copays, and (4) out-of-pocket maximums. Multivariate linear regression was used to assess differences in performance by specialty, adjusting for attitudes toward cost conversations, demographics, and clinical characteristics.ResultsThe response rate was 45% (405 of 900) and 371 respondents met inclusion criteria. Among the respondents included in this study, 59% (n = 220) identified as male, 23% (n = 84) as Asian, 3% (n = 12) as Black, 6% (n = 24) as Hispanic, and 58% (n = 216) as White; 30% (n = 112) were primary care physicians, 35% (n = 128) were gastroenterologists, and 35% (n = 131) were rheumatologists; and the mean (SD) age was 49 (10) years. Overall, 52% of physicians (n = 192) accurately estimated costs before the deductible was met, 62% (n = 228) accurately used coinsurance information, 61% (n = 224) accurately used copay information, and 57% (n = 210) accurately estimated costs once the out-of-pocket maximum was met. Only 21% (n = 78) of physicians answered all 4 questions correctly. Ability to estimate out-of-pocket costs was not associated with specialty, attitudes toward cost conversations, or clinic characteristics.Conclusions and relevanceThis survey study found that many US physicians have difficulty estimating out-of-pocket costs, even when they have access to their patients' insurance plans. The mechanics involved in calculating real-time out-of-pocket costs are complex. These findings suggest that increased price transparency and simpler insurance cost-sharing mechanisms are needed to enable informed cost conversations at the point of prescribing.

Project description:The protein kinase family is large and important, but it is only one family in a larger superfamily of homologous kinases that phosphorylate a variety of substrates and play important roles in all three superkingdoms of life. We used a carefully constructed structural alignment of selected kinases as the basis for a study of the structural evolution of the protein kinase-like superfamily. The comparison of structures revealed a "universal core" domain consisting only of regions required for ATP binding and the phosphotransfer reaction. Remarkably, even within the universal core some kinase structures display notable changes, while still retaining essential activity. Hence, the protein kinase-like superfamily has undergone substantial structural and sequence revision over long evolutionary timescales. We constructed a phylogenetic tree for the superfamily using a novel approach that allowed for the combination of sequence and structure information into a unified quantitative analysis. When considered against the backdrop of species distribution and other metrics, our tree provides a compelling scenario for the development of the various kinase families from a shared common ancestor. We propose that most of the so-called "atypical kinases" are not intermittently derived from protein kinases, but rather diverged early in evolution to form a distinct phyletic group. Within the atypical kinases, the aminoglycoside and choline kinase families appear to share the closest relationship. These two families in turn appear to be the most closely related to the protein kinase family. In addition, our analysis suggests that the actin-fragmin kinase, an atypical protein kinase, is more closely related to the phosphoinositide-3 kinase family than to the protein kinase family. The two most divergent families, alpha-kinases and phosphatidylinositol phosphate kinases (PIPKs), appear to have distinct evolutionary histories. While the PIPKs probably have an evolutionary relationship with the rest of the kinase superfamily, the relationship appears to be very distant (and perhaps indirect). Conversely, the alpha-kinases appear to be an exception to the scenario of early divergence for the atypical kinases: they apparently arose relatively recently in eukaryotes. We present possible scenarios for the derivation of the alpha-kinases from an extant kinase fold.

Dataset Information

Filling out the structural map of the NTF2-like superfamily.

Background

Results

Conclusions

Publications

Filling out the structural map of the NTF2-like superfamily.

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