A dimeric catalytic core relates the short and long forms of ATP-phosphoribosyltransferase

2018 ◽  
Vol 475 (1) ◽  
pp. 247-260 ◽  
Author(s):  
Gerd Mittelstädt ◽  
Wanting Jiao ◽  
Emma K. Livingstone ◽  
Gert-Jan Moggré ◽  
Ali Reza Nazmi ◽  
...  

Adenosine triphosphate (ATP) phosphoribosyltransferase (ATP-PRT) catalyses the first committed step of histidine biosynthesis in plants and microorganisms. Two forms of ATP-PRT have been reported, which differ in their molecular architecture and mechanism of allosteric regulation. The short-form ATP-PRT is a hetero-octamer, with four HisG chains that comprise only the catalytic domains and four separate chains of HisZ required for allosteric regulation by histidine. The long-form ATP-PRT is homo-hexameric, with each chain comprising two catalytic domains and a covalently linked regulatory domain that binds histidine as an allosteric inhibitor. Here, we describe a truncated long-form ATP-PRT from Campylobacter jejuni devoid of its regulatory domain (CjeATP-PRTcore). Results showed that CjeATP-PRTcore is dimeric, exhibits attenuated catalytic activity, and is insensitive to histidine, indicating that the covalently linked regulatory domain plays a role in both catalysis and regulation. Crystal structures were obtained for CjeATP-PRTcore in complex with both substrates, and for the first time, the complete product of the reaction. These structures reveal the key features of the active site and provide insights into how substrates move into position during catalysis.

2005 ◽  
Vol 17 (9) ◽  
pp. 68
Author(s):  
G. Gibori ◽  
J. Halpern ◽  
C. Stocco ◽  
P. Kelly ◽  
N. Binart

Extensive investigations from our laboratory have clarified the action and interaction of estradiol (E) and prolactin (PRL) on corpus luteum (CL) function. Our research has led us to discover and isolate a CL specific gene that encodes a protein we named PRAP, that associates with the intracellular domain of the short form (PRLRS) but not the long form (PRLRL) and whose expression is tightly regulated by E. Our laboratory and others have established that this protein, expressed in CL of every species investigated, is a novel 17 beta hydroxysteroid dehydrogenase (17bHSD-7) whose function is to catalyze the transformation of estrone to E. Our results with cells expressing only PRLRS revealed that PRL acting through PRLRS leads to phosphorylation of PRAP/17bHSD-7 (PRAP/17b) by JAK2 establishing for the first time that a steroidogenic enzyme can be phosphorylated through its association with a membrane bound protein. The association of PRAP/17b with the PRLRS and its phosphorylation leads to its stabilization. To further investigate the role of PRL signaling through PRLRS, we used PRLR(–/–) mice expressing the PRLRS as a transgene. The results obtained were totally unexpected and of great interest. The follicles of the ovaries, expressing PRLRS only, underwent premature development followed by severe granulosa and oocyte death leaving holes surrounding collapsed zona pellucida and premature ovarian failure. The observations that: (1) the expression of PRLRS in the ovaries of PRL null mice leads to inhibition in Foxo3a and of GALT, two proteins whose deletion/mutation causes similar premature ovarian failure; and (2) that GALT promoter activity is stimulated by Foxo3a transcription factor led us to hypothesize that PRL acting through PRLRS prevents the expression of Foxo3a, which normally stimulates GALT transcriptional activity. Absence of Foxo3a then leads to inhibition of GALT and increases in galactose and its metabolites, causing galactose toxicity and granulosa as well as oocyte cell death.


2017 ◽  
Vol 61 (4) ◽  
pp. 205-216 ◽  
Author(s):  
Kanako Iwanaga ◽  
John Blake ◽  
Rana Yaghmaian ◽  
Emre Umucu ◽  
Fong Chan ◽  
...  

The purpose of this study was to develop and validate a short-form version of the Attachment Style Questionnaire (ASQ) in people with disabilities. The construction sample consisted of 108 participants recruited from spinal cord injury (SCI) advocacy organizations. The cross-validation sample comprised 140 individuals with traumatic injuries recruited from a rehabilitation hospital. Measures administered were the ASQ, Trait Hope Scale, Sense of Coherence Scale, and Satisfaction With Life Scale. Results showed that the three subscales of secure, anxious, and avoidant attachment from the short-form ASQ had high correlations with the three subscales from the long-form ASQ. The reliability of the subscales for the short-form ASQ was adequate and similar to the long-form ASQ. Both the short- and long-form ASQ subscales were found to correlate with hope, sense of coherence, and subjective well-being in the expected theoretical directions. Confirmatory factor analysis also supported the three-factor measurement structure of the short-form ASQ. This study provides evidence to support the psychometric properties of the abbreviated ASQ in people with disabilities. The short-form version of the ASQ is a brief, reliable, and psychometrically sound measure of attachment that can be used in clinical rehabilitation counseling research and practice.


2018 ◽  
Vol 115 (45) ◽  
pp. 11483-11488 ◽  
Author(s):  
Niklas Harder ◽  
Lucila Figueroa ◽  
Rachel M. Gillum ◽  
Dominik Hangartner ◽  
David D. Laitin ◽  
...  

The successful integration of immigrants into a host country’s society, economy, and polity has become a major issue for policymakers in recent decades. Scientific progress in the study of immigrant integration has been hampered by the lack of a common measure of integration, which would allow for the accumulation of knowledge through comparison across studies, countries, and time. To address this fundamental problem, we propose the Immigration Policy Lab (IPL) Integration Index as a pragmatic and multidimensional measure of immigrant integration. The measure, both in the 12-item short form (IPL-12) and the 24-item long form (IPL-24), captures six dimensions of integration: psychological, economic, political, social, linguistic, and navigational. The measure can be used across countries, over time, and across different immigrant groups and can be administered through short questionnaires available in different modes. We report on four surveys we conducted to evaluate the empirical performance of our measure. The tests reveal that the measure distinguishes among immigrant groups with different expected levels of integration and also correlates with well-established predictors of integration.


2018 ◽  
Author(s):  
Debnath Ghosal ◽  
Yi-Wei Chang ◽  
Kwang Cheol Jeong ◽  
Joseph P. Vogel ◽  
Grant J. Jensen

AbstractLegionella pneumophilasurvives and replicates inside host cells by secreting ~300 effectors through the Dot/Icm type IVB secretion system (T4BSS). Understanding this machine’s structure is challenging because of its large number of components (27) and integration into all layers of the cell envelope. Previously we overcame this obstacle by imaging the Dot/Icm T4BSS in its native state within intact cells through electron cryotomography. Here we extend our observations by imaging a stabilized mutant that yielded a higher resolution map. We describe for the first time the presence of a well-ordered central channel that opens up into a windowed large (~32 nm wide) secretion chamber with an unusual 13-fold symmetry. We then dissect the complex by matching proteins to densities for many components, including all those with periplasmic domains. The placement of known and predicted structures of individual proteins into the map reveals the architecture of the T4BSS and provides a roadmap for further investigation of this amazing specialized secretion system.


2000 ◽  
Vol 113 (11) ◽  
pp. 2023-2034 ◽  
Author(s):  
N.V. Hayes ◽  
C. Scott ◽  
E. Heerkens ◽  
V. Ohanian ◽  
A.M. Maggs ◽  
...  

It is established that variations in the structure and activities of betaI spectrin are mediated by differential mRNA splicing. The two betaI spectrin splice forms so far identified have either long or short C-terminal regions. Are analogous mechanisms likely to mediate regulation of betaII spectrins? Thus far, only a long form of betaII spectrin is reported in the literature. Five human expressed sequence tags indicated the existence of a short splice variant of betaII spectrin. The occurrence and DNA sequence of the short C-terminal variant was confirmed by analysis of human and rat cDNA. The novel variant lacks a pleckstrin homology domain, and has 28 C-terminal residues not present in the previously recognized longer form. Transcripts of the short C-terminal variant (7.5 and 7. 0 kb) were most abundant in tissues originating from muscle and nervous system. Antibodies raised to a unique sequence of short C-terminal variant recognized 240 kDa polypeptides in cardiac and skeletal muscle and in nervous tissue; in cerebellum and forebrain, additional 270 kDa polypeptides were detected. In rat heart and skeletal muscle, both long and short C-terminal forms of betaII spectrin localized in the region of the Z line. The central region of the sarcomere, coincident with the M line, was selectively labeled with antibodies to the short C-terminal form. In cerebellum, the short form was not detectable in parallel fibers, structures in which the long form was readily detected. In cultured cerebellar granule neurons, the long form was dominant in neurites, with the short form being most abundant in cell bodies. In vitro, the short form was found to lack the binding activity for the axonal protein fodaxin, which characterizes the C-terminal region of the long form. Subcellular fractionation of brain revealed that the short form was scarcely detectable in post-synaptic density preparations, in which the long form was readily detected. We conclude that variation in the structure of the C-terminal regions of betaII spectrin isoforms correlates with their differential intracellular targeting.


Author(s):  
Andrew Hui

This epilogue explores Twitter, which was founded in 2006, launching the now ubiquitous platform of the 140-character short form (now enlarged to 280). It is not difficult to see Twitter as a digital descendant of the analog aphorism. However, the ecosystem of twitterature embraces more: it is a vehicle also for journalism, advertising, corporate communication, self-promotion, political campaigns, experimental poetry, micro short stories, collaborative works, and rewritings of the classics. In terms of this book's theory of the aphorism, tweets come before, after, and against long-form publications. Sometimes they function as headlines or clickbaits that link to longer forms of continuous writing. And in terms of the book's central conceptual paradigm—fragments and systems—Twitter offers both on an exponentially larger and faster scale.


2020 ◽  
Vol 25 (4) ◽  
pp. 759-771
Author(s):  
Philipp E. Chetverikov ◽  
James W. Amrine Jr. ◽  
Enikő Kiss ◽  
Jenő Kontschán ◽  
Géza Ripka

It is widely accepted in literature that members of Diptilomiopidae possess a “long-form” oral stylet which is usually nearly as long as the cheliceral stylets. However, it is not only the length of the oral stylet itself that is the character to discriminate diptilomiopids, but also its shape and the orientation of the pharynx. We reinvestigated the gnathosoma of Rhyncaphytoptus longipalpis Xue et Hong, 2005, a “diptilomiopid” species from China, and demonstrated that this mite has an angled short-form oral stylet and an almost horizontally oriented pharynx, which is not typical for Diptilomiopidae. We reassign “longipalpis” to a new genus Bambusacarus n. gen. in a different family-group (Eriophyidae, Phyllocoptinae, Anthocoptini) and provide a supplementary description of this species based on the material from Hungary where it was found on six introduced bamboo species of the genus Phyllostachys (Poaceae). Similar to members of endoparasitic genus Novophytoptus (Phytoptidae), B. longipalpis n. comb. has elongate, forceps-shaped gnathosomal structures and it lacks setae d and v on palps. We conclude that in some “non-diptlilomiopid” lineages of Eriophyoidea (1) the elongation of palps and changing of the length and curvature of the gnathosomal stylets may not be correlated with transformation of the shape of the oral stylet and reorientation of pharynx, and (2) when this happens, the mite homoplastically acquires the well-recognized “diptilomiopid-like” phenotype as seen in B. longipalpis n. comb. In future, careful reinvestigation of the shape of the oral stylet in Diptilomiopidae may reveal new examples of similar phenotypic convergency in Eriophyoidea.


2003 ◽  
Vol 284 (3) ◽  
pp. R763-R770 ◽  
Author(s):  
Abram M. Madiehe ◽  
Tiffany D. Mitchell ◽  
Ruth B. S. Harris

Leptin deficiency in ob/ob mice increases susceptibility to endotoxic shock, whereas leptin pretreatment protects them against LPS-induced lethality. Lack of the long-form leptin receptor (Ob-Rb) in db/db mice causes resistance. We tested the effects of LPS in C57BL/6J db3J/db3J (BL/3J) mice, which express only the circulating leptin receptors, compared with C57BL/6J db/db (BL/6J) mice, which express all short-form and circulating isoforms of the leptin receptor. Intraperitoneal injections of LPS significantly decreased rectal temperature and increased leptin, corticosterone, and free TNF-α in fed and fasted BL/3J and BL/6J mice. TNF-α was increased three- and fourfold in BL/3J and BL/6J, respectively. LPS (100 μg) caused 50% mortality of fasted BL/6J mice but caused no mortality in fasted BL/3J mice. Pretreatment of fasted BL/3J mice with 30 μg leptin prevented the drop in rectal temperature, blunted the increase in corticosterone, but had no effect on TNF-α induced by 100 μg LPS. Taken together, these data provide evidence that fasted BL/3J mice are more resistant than BL/6J mice to LPS toxicity, presumably due to the absence of leptin receptors in BL/3J mice. This resistance may be due to high levels of free leptin cross-reacting with other cytokine receptors.


2019 ◽  
Vol 24 (9) ◽  
pp. 1631-1652
Author(s):  
Philipp Chetverikov ◽  
S.J. Bolton ◽  
M.S. Burlakovskiy ◽  
C. Craemer ◽  
P.G. Efimov ◽  
...  

New records and supplementary morphological descriptions of two rarely encountered Trisetacus species from Pinaceae, T. abietis Postner 1968 and T. cedri (Nalepa 1920), are reported. Trisetacus abietis was found in Abkhazia under the needle epidermis of Abies nordmanniana (Steven) Spach, a conifer endemic to the mountainous Asian coast of the Black Sea. Trisetacus cedri was found in buds of introduced Cedrus deodara (Roxb. ex D. Don) G. Don in Abkhazia and South Africa. It is the only member of Trisetacus known from Cedrus spp. For the first time we provide sequences of two genes (COI and D1–D2 28S) of T. abietis (MN022221, MN025333) and T. cedri (MN022222, MN022223, MN025334, MN025335), along with microphotographs of the damage caused by these mites on their coniferous hosts. Sequences of D1–D2 28S of T. cedri from Abkhazian and South African populations are identical; COI sequences from different populations differ by only one synonymous substitution in a codon for asparagine. Females of T. abietis have long asymmetrical 8/7-rayed empodia, whereas males have shorter symmetrical 6/6-rayed empodia and shorter solenidia ω I. Similar sexual dimorphism in tarsal appendages was previously reported in Novophytoptus, representing an endoparasitic lineage of phytoptids on monocots. In T. cedri, a “long form” and a “short form” of both males and females were detected, suggesting a complex life cycle in this species. The evolution of Trisetacus is discussed within the broader context of the molecular phylogenies of Pinaceae and Eriophyoidea, including estimations of divergence times.


Sign in / Sign up

Export Citation Format

Share Document