Abstract
We present a comprehensive study of Z CVn, an RR Lyrae star that shows long-term cyclic variations of its pulsation period. A possible explanation suggested from the shape of the O−C diagram ...is the light travel-time effect, which we thoroughly examine. We used original photometric and spectroscopic measurements and investigated the period evolution using available maximum times spanning more than one century. If the binary hypothesis is valid, Z CVn orbits around a black hole with minimal mass of 56.5 $\mathfrak {M}_{{\odot }}$ on a very wide (Porbit = 78.3 yr) and eccentric orbit (e = 0.63). We discuss the probability of the formation of a black hole–RR Lyrae pair, and, although we found it possible, there is no observational evidence of the black hole in the direction to Z CVn. However, the main objection against the binary hypothesis is the comparison of the systemic radial velocity curve model and spectroscopic observations that clearly show that Z CVn cannot be bound in such a binary. Therefore, the variations of pulsation period are likely intrinsic to the star. This finding represents a discovery/confirmation of a new type of cyclic period changes in RR Lyrae stars. By the analysis of our photometric data, we found that the Blazhko modulation with period of 22.931 d is strongly dominant in amplitude. The strength of the phase modulation varies and is currently almost undetectable. We also estimated photometric physical parameters of Z CVn and investigated their variations during the Blazhko cycle using the inverse Baade–Wesselink method.
WW Camelopardalis is a relatively bright eclipsing binary system with a slightly eccentric orbit. A dozen of its new eclipse times were measured as part of our long-term observational project of ...eccentric eclipsing binaries. Based on a new solution of the current O -- C diagram, we found for the first time an apsidal motion in good agreement with theory. Its period is about 370 ? 50 years. The determined internal structure constant is close to the theoretically expected value. The relativistic effect is significant, being about 13% of the total apsidal motion rate.
Many RR Lyrae stars show long-term variations of their pulsation period, some of them in a cyclic way. Such behaviour can be attributed to the light-travel time effect (LTTE) caused by an unseen ...companion. Solutions of the LTTE often suggest very eccentric orbits and minimal mass of the companion on the order of several solar masses, thus, in the black hole range. We discuss the possibility of the occurrence of the RR Lyr-black hole pairs and on the case of Z CVn demonstrate that the LTTE hypothesis can be false in some of the binary candidates.
WW Camelopardalis is a relatively bright eclipsing binary system with a slightly eccentric orbit. A dozen of its new eclipse times were measured as part of our long-term observational project of ...eccentric eclipsing binaries. Based on a new solution of the current O - C diagram, we found for the first time an apsidal motion in good agreement with theory. Its period is about 370 {+-} 50 years. The determined internal structure constant is close to the theoretically expected value. The relativistic effect is significant, being about 13% of the total apsidal motion rate.
We present a comprehensive study of Z CVn, an RR Lyrae star that shows long-term cyclic variations of its pulsation period. A possible explanation suggested from the shape of the O-C diagram is the ...light travel-time effect, which we thoroughly examine. We used original photometric and spectroscopic measurements and investigated the period evolution using available maximum times spanning more than one century. If the binary hypothesis is valid, Z CVn orbits around a black hole with minimal mass of \(56.5\) \(\mathfrak{M}_{\odot}\) on a very wide (\(P_{\rm orbit}=78.3\) years) and eccentric orbit (\(e=0.63\)). We discuss the probability of a formation of a black hole-RR Lyrae pair and, although we found it possible, there is no observational evidence of the black hole in the direction to Z CVn. However, the main objection against the binary hypothesis is the comparison of the systemic radial velocity curve model and spectroscopic observations that clearly show that Z CVn cannot be bound in such a binary. Therefore, the variations of pulsation period are likely intrinsic to the star. This finding represents a discovery/confirmation of a new type of cyclic period changes in RR Lyrae stars. By the analysis of our photometric data, we found that the Blazhko modulation with period of 22.931 d is strongly dominant in amplitude. The strength of the phase modulation varies and is currently almost undetectable. We also estimated photometric physical parameters of Z CVn and investigated their variations during the Blazhko cycle using the Inverse Baade-Wesselink method.
Cross-talk between distinct protein post-translational modifications is critical for an effective DNA damage response. Arginine methylation plays an important role in maintaining genome stability, ...but how this modification integrates with other enzymatic activities is largely unknown. Here, we identify the deubiquitylating enzyme USP11 as a previously uncharacterised PRMT1 substrate, and demonstrate that the methylation of USP11 promotes DNA end-resection and the repair of DNA double strand breaks (DSB) by homologous recombination (HR), an event that is independent from another USP11-HR activity, the deubiquitylation of PALB2. We also show that PRMT1 is a ubiquitylated protein that it is targeted for deubiquitylation by USP11, which regulates the ability of PRMT1 to bind to and methylate MRE11. Taken together, our findings reveal a specific role for USP11 during the early stages of DSB repair, which is mediated through its ability to regulate the activity of the PRMT1-MRE11 pathway.
The contact system is composed of factor XII (FXII), prekallikrein (PK), and cofactor high-molecular-weight kininogen (HK). The globular C1q receptor (gC1qR) has been shown to interact with FXII and ...HK. We reveal the FXII fibronectin type II domain (FnII) binds gC1qR in a Zn2+-dependent fashion and determined the complex crystal structure. FXIIFnII binds the gC1qR trimer in an asymmetric fashion, with residues Arg36 and Arg65 forming contacts with 2 distinct negatively charged pockets. gC1qR residues Asp185 and His187 coordinate a Zn2+ adjacent to the FXII-binding site, and a comparison with the ligand-free gC1qR crystal structure reveals the anionic G1-loop becomes ordered upon FXIIFnII binding. Additional conformational changes in the region of the Zn2+-binding site reveal an allosteric basis for Zn2+ modulation of FXII binding. Mutagenesis coupled with surface plasmon resonance demonstrate the gC1qR Zn2+ site contributes to FXII binding, and plasma-based assays reveal gC1qR stimulates coagulation in a FXII-dependent manner. Analysis of the binding of HK domain 5 (HKD5) to gC1qR shows only 1 high-affinity binding site per trimer. Mutagenesis studies identify a critical G3-loop located at the center of the gC1qR trimer, suggesting steric occlusion as the mechanism for HKD5 asymmetric binding. Gel filtration experiments reveal that gC1qR clusters FXII and HK into a higher-order 500-kDa ternary complex. These results support the conclusion that extracellular gC1qR can act as a chaperone to cluster contact factors, which may be a prelude for initiating the cascades that drive bradykinin generation and the intrinsic pathway of coagulation.
Metabolic networks are interconnected and influence diverse cellular processes. The protein-metabolite interactions that mediate these networks are frequently low affinity and challenging to ...systematically discover. We developed mass spectrometry integrated with equilibrium dialysis for the discovery of allostery systematically (MIDAS) to identify such interactions. Analysis of 33 enzymes from human carbohydrate metabolism identified 830 protein-metabolite interactions, including known regulators, substrates, and products as well as previously unreported interactions. We functionally validated a subset of interactions, including the isoform-specific inhibition of lactate dehydrogenase by long-chain acyl-coenzyme A. Cell treatment with fatty acids caused a loss of pyruvate-lactate interconversion dependent on lactate dehydrogenase isoform expression. These protein-metabolite interactions may contribute to the dynamic, tissue-specific metabolic flexibility that enables growth and survival in an ever-changing nutrient environment.
Essentials
Zymogen PK is activated to PKa and cleaves substrates kininogen and FXII contributing to bradykinin generation.
Monomeric PKa and dimeric homologue FXI utilize the N‐terminal apple domains ...to recruit substrates.
A high‐resolution 1.3 Å structure of full‐length PKa reveals an active conformation of the protease and apple domains.
The PKa protease and four‐apple domain disc organization is 180° rotated compared to FXI.
Summary
Background
Plasma prekallikrein (PK) and factor XI (FXI) are apple domain‐containing serine proteases that when activated to PKa and FXIa cleave substrates kininogen, factor XII, and factor IX, respectively, directing plasma coagulation, bradykinin release, inflammation, and thrombosis pathways.
Objective
To investigate the three‐dimensional structure of full‐length PKa and perform a comparison with FXI.
Methods
A series of recombinant full‐length PKa and FXI constructs and variants were developed and the crystal structures determined.
Results and conclusions
A 1.3 Å structure of full‐length PKa reveals the protease domain positioned above a disc‐shaped assemblage of four apple domains in an active conformation. A comparison with the homologous FXI structure reveals the intramolecular disulfide and structural differences in the apple 4 domain that prevents dimer formation in PK as opposed to FXI. Two latchlike loops (LL1 and LL2) extend from the PKa protease domain to form interactions with the apple 1 and apple 3 domains, respectively. A major unexpected difference in the PKa structure compared to FXI is the 180° disc rotation of the apple domains relative to the protease domain. This results in a switched configuration of the latch loops such that LL2 interacts and buries portions of the apple 3 domain in the FXI zymogen whereas in PKa LL2 interacts with the apple 1 domain. Hydrogen‐deuterium exchange mass spectrometry on plasma purified human PK and PKa determined that regions of the apple 3 domain have increased surface exposure in PKa compared to the zymogen PK, suggesting conformational change upon activation.
PDF
