Functional Diversity and Structural Disorder in the Human Ubiquitination Pathway

The ubiquitin-proteasome system plays a central role in cellular regulation and protein quality control (PQC). The system is built as a pyramid of increasing complexity, with two E1 (ubiquitin activating), few dozen E2 (ubiquitin conjugating) and several hundred E3 (ubiquitin ligase) enzymes. By collecting and analyzing E3 sequences from the KEGG BRITE database and literature, we assembled a coherent dataset of 563 human E3s and analyzed their various physical features. We found an increase in structural disorder of the system with multiple disorder predictors (IUPred - E1: 5.97%, E2: 17.74%, E3: 20.03%). E3s that can bind E2 and substrate simultaneously (single subunit E3, ssE3) have significantly higher disorder (22.98%) than E3s in which E2 binding (multi RING-finger, mRF, 0.62%), scaffolding (6.01%) and substrate binding (adaptor/substrate recognition subunits, 17.33%) functions are separated. In ssE3s, the disorder was localized in the substrate/adaptor binding domains, whereas the E2-binding RING/HECT-domains were structured. To demonstrate the involvement of disorder in E3 function, we applied normal modes and molecular dynamics analyses to show how a disordered and highly flexible linker in human CBL (an E3 that acts as a regulator of several tyrosine kinase-mediated signalling pathways) facilitates long-range conformational changes bringing substrate and E2-binding domains towards each other and thus assisting in ubiquitin transfer. E3s with multiple interaction partners (as evidenced by data in STRING) also possess elevated levels of disorder (hubs, 22.90% vs. non-hubs, 18.36%). Furthermore, a search in PDB uncovered 21 distinct human E3 interactions, in 7 of which the disordered region of E3s undergoes induced folding (or mutual induced folding) in the presence of the partner. In conclusion, our data highlights the primary role of structural disorder in the functions of E3 ligases that manifests itself in the substrate/adaptor binding functions as well as the mechanism of ubiquitin transfer by long-range conformational transitions. © 2013 Bhowmick et al

The 6^{6}H states studied in the d(8He,α)d(^8\text{He},\alpha) reaction and evidence of extremely correlated character of the 5^{5}H ground state

The extremely neutron-rich system $^{6}$H was studied in the direct $^2\text{H}(^8\text{He},{^4\text{He}})^{6}$H transfer reaction with a 26 $A$ MeV secondary $^{8}$He beam. The measured missing mass spectrum shows a resonant state in $^{6}$H at $6.8(3)$ MeV relative to the $^3$H+$3n$ threshold. The population cross section of the presumably $p$-wave states in the energy range from 4 to 8 MeV is $d\sigma/d\Omega_{\text{c.m.}} \simeq 190(40)$ $\mu$b/sr in the angular range $5^{\circ}<\theta_{\text{c.m.}}<16^{\circ}$. The obtained missing mass spectrum is free of the $^{6}$H events below 3.5 MeV ($d\sigma/d\Omega_{\text{c.m.}} \lesssim 3$ $\mu$b/sr in the same angular range). The steep rise of the $^{6}$H missing mass spectrum at 3 MeV allows to show that $4.5(3)$ MeV is the lower limit for the possible resonant state energy in $^{6}$H tolerated by our data. According to paring energy estimates, such a $4.5(3)$ MeV resonance is a realistic candidate for the $^{6}$H ground state (g.s.). The obtained results confirm that the decay mechanism of the $^{7}$H g.s.\ (located at 2.2 MeV above the $^{3}$H+$4n$ threshold) is the ``true'' (or simultaneous) $4n$ emission. The resonance energy profiles and the momentum distributions of the sequential $^{6}$H \,\rightarrow \, ^5H(g.s.)+n\, \rightarrow \, ^3H+$3n$ decay fragments were analyzed by the theoretically-updated direct four-body-decay and sequential-emission mechanisms. The measured momentum distributions of the $^{3}$H fragments in the $^{6}$H rest frame indicate very strong ``dineutron-type'' correlations in the $^{5}$H ground state decay.Comment: 9 pages, 11 figure

Study of Proton and Deuteron Pickup Reactions 2H(10Be,3He)9Li an 2H(10Be,4He)8Li with 44 A MeV 10Be Radioactive Beam at ACCULINNA-2 Fragment Separator

The proton and deuteron pickup reactions 2H(10Be,3He)9Li and\\ 2H(10Be,4He)8Li radioactive beam produced by the new fragment separator ACCULINNA-2 at FLNR, JINR\@. These measurements were initially motivated as test reactions intended for the elucidation of results obtained in the study of the extremely neutron-rich 7H and 6H systems created in the 2H(10Be,3He)9Li and 2H(10Be,4He)8Li reactions using the same setup. In the 2H(10Be,3He)9Li reaction the 9Li ground-state ($3/2^-$) and its first excited state (2.69~MeV, $1/2^-$) were identified in the low-energy region of its excitation spectrum. The differential cross sections for the 9Li g.~s.) population were extracted at forward center-of-mass angles ($3^\circ-13^\circ$) and compared with the FRESCO calculations. Spectroscopic factor of $\sim 1.7$, derived by a model for the 10Be$= p +$9Li(g.s.) clustering was found in accord with the experimental data. The energy spectrum of 8Li populated in the 2H(10Be,4He)8Li reaction shows the strong peak which corresponds to excitation of the second excited state of 8Li (2.25 MeV, $3^+$). The fact that the ground and the first excited states of 8Li were not observed is fully consistent with Shell-Model calculations carried out for the 10Be g.\,s. and 8Li level structure applying momentum selection rules

Fosfor przyswajalny w piaszczystych glebach pobagiennych Równiny Mazurskiej

Zawartość przyswajalnego fosforu oznaczona według metody Egnera-Riehma, jak również w roztworze HCl o stężeniu 0,5 mol·dm⁻³, wzrasta w badanych glebach w miarę zwiększania się zawartości materii organicznej. Kwas solny ekstrahuje średnio od 10 do 20 razy więcej fosforu niż roztwór mleczanu wapnia. W badanych glebach występują równocześnie fosforany wapnia i żelaza, lecz fosforanów żelaza jest więcej. Gleby pobagienne zasobne w tlenki żelaza wykazują bardzo wysoką zawartość fosforu ekstrahowanego HCl, lecz ich zasobność oznaczona metodą Egnera-Riehma jest niska, co należy uwzględnić przy mineralnym odżywianiu roślin.The content of available phosphorus determined by the Egner-Riehm’s method as well as the phosphorus content determined in 0.5 mol HCl soil extract increases hi the investigated soils with the increase of organic matter content. The HCl solution extracts from 10 to 20 times more phosphorus than calcium lactate solution (DL). In the investigated soils the calcium phosphates and the iron phosphates occur simultaneously, but the amount of the later is greater. The post-boggy soils which are rich in iron oxides have very high content of the HCl - soluble phosphorus, but their phosphorus abundance determined by the Egner-Riehm’s method is low. This should be taken into consideration in mineral plant nutrition