UniProt ID Research Articles

Structural basis for a ribofuranosyl binding protein: Insights into the furanose specific transport

The ATP-binding cassette transporters (ABC-transporters) are members of one of the largest protein superfamilies, with representatives in all extant phyla1. These integral membrane proteins utilize the energy of ATP hydrolysis to carry out certain biological processes, including translocation of various substrates across membranes and non-transport related processes such as translation of RNA and DNA repair2. Typically, such transport systems in bacteria consist of an ATP binding component, a transmembrane permease, and a periplasmic receptor or binding protein. Soluble proteins found in the periplasm of gram-negative bacteria serve as the primary receptors for transport of many compounds, such as sugars, small peptides, and some ions. Ligand binding activates these periplasmic components, permitting recognition by the membrane spanning domain, which supports for transport and, in some cases, chemotaxis3-5. Transport and chemotaxis processes appear to be independent of one another, and a few mutants of bifunctional periplasmic components reveal the absence of one or the other function6. Previously published high-resolution X-ray structures of various periplasmic ligand binding proteins include Arabinose binding protein (ABP)7, Allose binding protein (ALBP)8, Glucose-galactose binding protein (GBP)9,10 and Ribose binding protein (RBP)11. Each of these proteins consists of two structurally similar domains connected by a three-stranded hinge region, with ligand buried between the domains. Upon ligand binding and release, various conformational changes have been observed12-14. For RBP, open (apo)15 and closed (ligand bound)14, 11 conformations have been reported and so for MBP16. The closed/active form of the protein interacts with the integral membrane component of the system in both transport and chemotaxis17. Herein, we report 1.9A resolution X-ray structure of the RfBP periplasmic component of an ABC-type sugar transport system from Hahella chejuensis (UniProt Id {type:entrez-protein,attrs:{text:Q2S7D2,term_id:123530140,term_text:Q2S7D2}}Q2S7D2) bound to the unusual furanose form of ribose.

Molecular Endocrinology: A Portal for Enhanced Access and Utility of the Nuclear Receptor Signaling Atlas (NURSA) Web Resource

This issue of Molecular Endocrinology features a minireview that describes the evolution and status of The Nuclear Receptor Signaling Atlas (NURSA). This National Institutes of Health-sponsored consortium was launched in 2002 to generate high-content, discovery-driven research datasets as a platform for developing an understanding of the role of nuclear receptors and coregulators in normal metabolic processes and pathologies. It was charged with integrating its research output of these component projects into an informatics framework and a supporting website for distributing the datasets and their analyses to the wider research community. A second, equally important challenge was to leverage legacy knowledge in the nuclear receptor and coregulator field and integrate it with Consortium datasets to create a unique resource that would be accessible to the entire scientific community. In addition to the support of the community, NURSA’s success relies on forging partnerships with the existing publishing infrastructure in the field. To this end, the NURSA consortium and Molecular Endocrinology have entered a partnership that is unique in scientific publishing. Specifically, in 2006, an agreement was made in which the NURSA curation team would annotate relevant Molecular Endocrinology articles back to 2002. These annotations would then be used to create direct links to NURSA Molecule Pages from the web versions of the articles, providing readers with a wealth of contextual information on a molecule relevant to that article. The NURSA Molecule Page is designed to integrate in a condensed, easily navigated form the essential elements of the mechanism, biology, and pathology of nuclear receptors, their coregulators, and their ligands. Recognizing that retrieving nuclear receptor- and coregulator-specific information in monolithic biological databases like NCBI and UniProt can be a daunting prospect, NURSA curators sifted these resources, gleaned the most important and essential descriptors (GeneID, UniProt ID, RefSeqs), and spliced them together in a single menu-driven interface. In addition, the Molecule Pages tie in relevant content from smaller specialist databases such as those curating crystal structures (PDB), splicing events (FastDB), expression (MousePAT, Allen Brain Atlas), and posttranslational modifications (Phosphosite). The collaboration between Molecular Endocrinology and NURSA also includes features designed to aid basic researchers in identifying translational aspects of their work. Specifically, the Molecule Page contains a distillation of databases documenting the key pathological associations of nuclear receptors and coregulators (HPRD, GAD, OMIM, in addition to NURSA’s own in-house curation) and the physiological consequences of their disruption in animal models. Finally, a new Google-powered search engine on the Molecule Page accommodates search strategies based on a specific disease or phenotype. The goals of the Molecule Page require the support of the research community, the National Institutes of Health, and The Endocrine Society. Accordingly, NURSA is developing features in the Molecule Pages that will afford motivated researchers to add to the NURSA knowledge base. Any of the components of the Molecule Pages that are based around literature citations will soon have built into them an interface in which a researcher can contribute articles for annotation. NURSA also welcomes the opportunity to host more extensive curational efforts. We urge all of our readers to visit and exploit the wealth of information available on the NURSA web site (www.nursa.org). Molecular Endocrinology is pleased to have been a part of this unique effort to enhance the accessibility and utility of comprehensive datasets to the field of endocrinology, and we look forward to new developments and resources provided by NURSA. In that regard, please look for a semiannual “What’s New in NURSA” editorial feature that will highlight new datasets and research tools provided by NURSA. We also hope to expand our journal’s role as a portal to other scientific collaborations and consortia that provide novel web-based datasets, informatics tools, and tutorials for the continued benefit of endocrinology research.

Websites of note

Websites of note

Identification of Apolipoprotein A-I as a “STOP” Signal for Myopia

Good visual acuity requires that the axial length of the ocular globe is matched to the refractive power of the cornea and lens to focus the images of distant objects onto the retina. During the growth of the juvenile eye, this is achieved through the emmetropization process that adjusts the ocular axial length to compensate for the refractive changes that occur in the anterior segment. A failure of the emmetropization process can result in either excessive or insufficient axial growth, leading to myopia or hyperopia, respectively. Emmetropization is mainly regulated by the retina, which generates two opposite signals: "GO/GROW" signals to increase axial growth and "STOP" signals to block it. The presence of GO/GROW and STOP signals was investigated by a proteomics analysis of the retinas from chicken with experimental myopia and hyperopia. Of 18 differentially expressed proteins that were identified, five displayed an expression profile corresponding to GO/GROW signals, and two corresponded to STOP signals. Western blotting confirmed that apolipoprotein A-I (apoA-I) has the characteristics of a STOP signal both in the retina as well as in the fibrous sclera. In accordance with this, intraocular application of the peroxisome proliferator-activated receptor alpha agonist GW7647 resulted in up-regulation of apoA-I levels and in a significant reduction of experimental myopia. In conclusion, using a comprehensive functional proteomics analysis of chicken ocular growth models we identified targets for ocular growth control. The correlation of elevated apoA-I levels with reduced ocular axial growth points toward a functional relationship with the observed morphological changes of the eye.