In a genetic screen, we identified two viable missense alleles of the essential gene Midnolin (Midn) that were associated with reductions in peripheral B cells. Causation was confirmed mice targeted deletion four six MIDN protein isoforms. expressed predominantly lymphocytes where it augmented proteasome activity. We showed purified directly stimulated 26S activity vitro manner dependent on ubiquitin-like domain and C-terminal region. MIDN-deficient cells displayed aberrant activation...

Plasma Alpha-1-glycoprotein (AGP) binds diverse drugs, its isoforms and their levels vary significantly in acute phases of health. Relative binding pattern drugs to AGP albumin has been used model release profiles, structural insights on glycosylated form will improve predictions. Main challenge is the heavy heterogeneous glycosylation molecules. Our small angle X-ray scattering (SAXS) data plasma extracted showed interparticulate effect from 283 313 K which disappeared irreversibly upon...

The protein midnolin (MIDN) augments proteasome activity in lymphocytes, where it is predominantly expressed adult mice. MIDN binds both to proteasomes and substrates, but the mechanism by which facilitates substrate degradation a ubiquitin-independent manner unknown. Here, we present cryo-electron microscopy structures of substrate-engaged, MIDN-bound human two conformational states. induces conformations similarly ubiquitinated substrates using its ubiquitin-like domain bind deubiquitinase...

DEAD-box ATPases play crucial roles in guiding rRNA restructuring events during the biogenesis of large (60S) ribosomal subunits, but their precise molecular functions are currently unknown. In this study, we present cryo-EM reconstructions nucleolar pre-60S intermediates that reveal an unexpected, alternate secondary structure within nascent peptidyl-transferase-center (PTC). Our analysis three sequential reveals ATPase Dbp10/DDX54 remodels base pairing and enables formation junction...

The study aims to map plasma gelsolin (pGSN) levels in diabetic humans and mice models of type II diabetes evaluate the efficacy therapy improvement mice. We report that pGSN values decrease by a factor 0.45 0.5 blood models. Oral glucose tolerance test showed subcutaneous administration recombinant its F-actin depolymerizing competent versions brought down sugar comparable Sitagliptin, drug used manage hyperglycemic condition. Further, daily dose or truncated for week kept close normal...

Gelsolin is a key actin cytoskeleton-modulating protein primarily regulated by calcium and phosphoinositides. In addition, low pH has also been suggested to activate gelsolin in the absence of Ca(2+) ions, although no structural insight on this pathway available except for reported decrement its diffusion coefficient at pH. We observed ~1.6-fold decrease molecular mobility recombinant when buffer was lowered from 9 5. Analysis small angle x-ray scattering data collected over same range...

Because of its ability to rapidly depolymerize F-actin, plasma gelsolin has emerged as a therapeutic molecule in different disease conditions. High amounts exogenous are, however, required treat animal models diseases. Knowing that the F-actin depolymerizing property resides N terminus, we made several truncated versions gelsolin. The smaller versions, particularly one composed first 28-161 residues, depolymerized much faster than native and other truncates at same molar ratios. Although...

HapR has been recognized as a quorum-sensing master regulator in Vibrio cholerae. Because it controls plethora of disparate cellular events, the absence functional affects physiology V. cholerae to great extent. In current study, we pursued an understanding observation natural protease-deficient non-O1, non-O139 variant strain V2. Intriguingly, nonfunctional (henceforth designated HapRV2) harboring substitution glycine aspartate at position 39 N-terminal hinge region identified. An vitro gel...

HapR has been given the status of a high cell density master regulatory protein in Vibrio cholerae. Though many facts are known regarding its structural and functional aspects, much still can be learnt from natural variants wild type protein. This work aims at investigating nature inertness variant harboring substitution conserved glutamate residue position 117 which participates forming salt bridge by lysine (HapRV2G-E117K). Experimental evidence presented here reveals inability this to...

Plasma gelsolin (pGSN), a protein primarily involved in clearance of circulating actin filaments, is an upcoming novel biomarker. Its level changes multiple disease and injury conditions, attributable mainly to its consumption during clearance; the endogenous regulation expression, however, remains elusive as well unexplored. Here, we are reporting first isolation promoter region pGSN gene investigation transcriptional pregnancy (a natural process associated with well-programmed course...

Plasma gelsolin (pGSN) is a multifunctional protein involved mainly in severing and clearing of actin filaments. Its level correlates with inflammation several diseases making it potential biomarker diagnostic prognostic values. The pGSN groups treated untreated HIV-1-infected Indian patients investigated this study. This study aims at investigating the levels across different age, sex, severity disease, treatment status. Blood samples 213 were analyzed for CD4 counts by flow cytometry was...

Abstract DEAD-box ATPases are ubiquitous enzymes essential in all aspects of RNA biology. However, the limited vitro catalytic activities described for these is at odds with their complex cellular roles, most notably driving large-scale remodeling steps during assembly ribonucleoproteins (RNPs). We describe cryo-EM structures 60S ribosomal biogenesis intermediates that reveal how context-specific unwinding by ATPase Spb4 results extensive, sequence-directed rRNA secondary structure. Multiple...

Plasma Alpha-1-glycoprotein (AGP) binds diverse drugs, its isoforms and their levels vary significantly in acute phases of health. Relative binding drugs to AGP albumin has been used model release profiles, structural insights on glycosylated form will certainly improve estimations. Main challenges are: 1) heavy glycosylation (~50% mass), 2) primary structure co-exist, 3) extreme heterogeneity the glycan motifs have reported. Our small angle X-ray scattering (SAXS) data plasma extracted...

ABSTRACT Structural insight eludes on how full-length gelsolin depolymerizes and caps F-actin, while the same entity can nucleate polymerization of G-actins. Employing small angle X-ray scattering (SAXS) data analysis, we deciphered these two contrasting assemblies. Mixing Ca 2+ -gelsolin with F-actin in high salt F-buffer resulted depolymerization ordered rods to smaller sized species which became monodisperse upon dialysis low G-buffer. These entities were ternary (GA 2 ) binary (GA)...

Abstract DEAD-box ATPases play crucial roles in guiding rRNA restructuring events during the biogenesis of large (60S) ribosomal subunits, but their precise molecular functions are currently unknown. In this study, we present cryo-EM reconstructions nucleolar pre-60S intermediates that reveal an unexpected, alternate secondary structure within nascent peptidyl-transferase-center (PTC). Our analysis three sequential reveals ATPase Dbp10/DDX54 remodels base pairing and enables formation...

Abstract Distinct pathways and molecules may support embryonic versus postnatal thymic epithelial cell (TEC) development maintenance. Here, we identify a mechanism by which TEC numbers function are maintained postnatally. A viable missense allele (C120Y) of Ovol2 , expressed ubiquitously or specifically in TECs, results lymphopenia, T is compromised loss medullary TECs dysfunction cortical TECs. We show that the identity aberrantly subverted towards mesenchymal state OVOL2-deficient mice....

Plasma gelsolin (pGSN) has been reported to decline in many diseases of humans as well animals. However, it is prerequisite know normal pGSN levels healthy animals so determine the dose need be given exogenously for repletion by replacement therapy. Therefore, purpose this study was quantify injury healing protein, different age (1, 3, 6 & 12 months) and sex (Male female) groups C57BL/6N mice Enzyme Linked Immunosorbent Assay (ELISA). Our results showed that average at one month were...