On Thaicypris panhai gen. et sp. nov., a new herpetocypridine ostracod (Crustacea: Ostracoda: Cyprididae) from Thailand

A new genus, Thaicypris gen. nov., in the tribe Herpetocypridini Kaufmann, 1900 of the subfamily Herpetocypridinae Kaufmann, 1900 is established to accommodate a new species from Thailand. The present contribution deals with the description of a new genus and species, Thaicypris panhai gen. et sp. nov., which is mainly characterized by the distinctive and raised, inwardly displaced selvage at the postero-ventral part of the right valve (RV) that is not parallel to the valve margin, the absence of an anterior inner list on the RV, the prominent and elevated double inner list on the posterior part of the left valve, the small and three-segmented Rome organ on the first antenna (A1), the spatulated terminal segment of the maxillular (Mx1) palp, the slender caudal ramus (CR) with long and thin Sp seta, the presence of basal triangle on the CR attachment, and the pointed projection at the terminal segment base of the prehensile palps. The hemipenis of the new genus and species is outstanding, especially the medial lateral shield which has a long, beak-shaped protrusion on the distal part. The discovery of this Thai taxon is the first record of the tribe Herpetocypridini in Thailand and the second species of the tribe in Southeast Asia.

Cryo-EM structure of an amyloid fibril formed by full-length human SOD1 reveals its pathological conformational conversion

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease characterized by the selective death of motor neurons. Misfolded Cu, Zn-superoxide dismutase (SOD1) has been linked to both familial ALS and sporadic ALS. SOD1 fibrils formed in vitro are able to incorporate into cells, transmit intercellularly, and share toxic properties with ALS inclusions. Here we produced amyloid fibrils in vitro from recombinant, full-length apo human SOD1 under semi-reducing conditions and determined the atomic structure using cryo-EM. The SOD1 fibril consists of a single protofibril with a left-handed helix. The fibril core exhibits a serpentine fold comprising N-terminal segment (residues 3 to 55) and C-terminal segment (residues 86 to 153) with a structural break. The two segments are zipped up by three salt bridge pairs. By comparison with the structure of apo SOD1 dimer, we propose that eight β-strands (to form a β-barrel) and one α-helix in the subunit of apo SOD1 convert into thirteen β-strands stabilized by five hydrophobic cavities in the SOD1 fibril. Our data provide insights into how SOD1 converts between structurally and functionally distinct states.

WFS1 functions in ER export of vesicular cargo proteins in pancreatic β-cells

The sorting of soluble secretory proteins from the endoplasmic reticulum (ER) to the Golgi complex is mediated by coat protein complex II (COPII) vesicles and thought to required specific ER membrane cargo-receptor proteins. However, these receptors remain largely unknown. Herein, we show that ER to Golgi transfer of vesicular cargo proteins requires WFS1, an ER-associated membrane protein whose loss of function leads to Wolfram syndrome. Mechanistically, WFS1 directly binds to vesicular cargo proteins including proinsulin via its ER luminal C-terminal segment, whereas pathogenic mutations within this region disrupt the interaction. The specific ER export signal encoded in the cytosolic N-terminal segment of WFS1 is recognized by the COPII subunit SEC24, generating mature COPII vesicles that traffic to the Golgi complex. WFS1 deficiency leads to abnormal accumulation of proinsulin in the ER, impeding the proinsulin processing as well as insulin secretion. This work identifies a vesicular cargo receptor for ER export and suggests that impaired peptide hormone transport underlies diabetes resulting from pathogenic WFS1 mutations.

PDZ-Containing Proteins Targeted by the ACE2 Receptor

Angiotensin-converting enzyme 2 (ACE2) is a main receptor for SARS-CoV-2 entry to the host cell. Indeed, the first step in viral entry is the binding of the viral trimeric spike (S) protein to ACE2. Abundantly present in human epithelial cells of many organs, ACE2 is also expressed in the human brain. ACE2 is a type I membrane protein with an extracellular N-terminal peptidase domain and a C-terminal collectrin-like domain that ends with a single transmembrane helix and an intracellular 44-residue segment. This C-terminal segment contains a PDZ-binding motif (PBM) targeting protein-interacting domains called PSD-95/Dlg/ZO-1 (PDZ). Here, we identified the human PDZ specificity profile of the ACE2 PBM using the high-throughput holdup assay and measuring the binding intensities of the PBM of ACE2 against the full human PDZome. We discovered 14 human PDZ binders of ACE2 showing significant binding with dissociation constants’ values ranging from 3 to 81 μM. NHERF, SHANK, and SNX27 proteins found in this study are involved in protein trafficking. The PDZ/PBM interactions with ACE2 could play a role in ACE2 internalization and recycling that could be of benefit for the virus entry. Interestingly, most of the ACE2 partners we identified are expressed in neuronal cells, such as SHANK and MAST families, and modifications of the interactions between ACE2 and these neuronal proteins may be involved in the neurological symptoms of COVID-19.

Legionella effector LegA15/AnkH contains an unrecognized cysteine protease-like domain and displays structural similarity to LegA3/AnkD, but differs in host cell localization

Legionella pneumophila is a human pathogen that causes Legionnaires' disease, a severe form of pneumonia. It can be found in various aquatic environments ranging from cooling towers to ponds. In addition to causing disease in humans, it can also infect free-living amoebae commonly found in various aquatic environments. Once inside a human lung macrophage, it creates a niche called the Legionella-containing vacuole where it can evade phagolysosomal degradation and replicate. During infection, normal cellular functions are hijacked by proteins that are secreted by the pathogen, called bacterial effectors. Here, the structural characterization of the effector LegA15/AnkD is reported. The protein contains an ankyrin-repeat domain followed by a cysteine protease-like (CPL) domain with a putative catalytic triad consisting of His268–Asn290–Cys361. The CPL domain shows similarity to the CE clan in the MEROPS database, which contains ubiquitin-like hydrolases. The C-terminal segment of LegA15, including the CPL domain, shows structural similarity to another effector, LegA3/AnkH, while they share only 12% sequence identity. When expressed in mammalian cells, LegA15 is localized within the cytoplasm, in contrast to LegA3, which localizes to the nucleus.

Study of the Operation Process of the E-Commerce Oriented Ecosystem of 5Ge Base Station, Which Supports the Functioning of Independent Virtual Network Segments

According to specifications, flexible services for traffic management should be implemented within the 5G platform in order to improve its efficiency, which is and will remain an actual task. For the first time, the article presented here proposes a mathematical model for the operation process of an e-commerce-oriented ecosystem of a 5Ge base station, the information environment of which supports the operation of independent virtual network segments that provide terminal–segment information interaction services. In contrast to existing models, the presented model describes the studied process as a multi-pipeline queuing system, the inputs of which are coordinated with the flows of requests for communication with the relevant virtual network segments. The distribution of the total resources between the weighted virtual network segments in the simulated system is dynamically conducted by the appropriate software control mechanism. It considers the address intensities of new incoming requests and the maintenance of received incoming requests, but throughout the scale of the information environment of the 5Ge base station ecosystem. Based on the created mathematical model, a functional algorithm for the forced termination of an active terminal–segment information interaction session in the overloaded virtual network segment and the control mechanism of the distribution of the released system resources between other virtual network segments that takes into account the degree of their overload are formulated. The simulation and computational experiments showed that the implemented forced termination algorithm and system resource management mechanism allow the 5Ge base station to continue receiving incoming requests despite the overload of individual virtual network segments. It is empirically shown that the proposed services are effectively scaled concerning the value that is generally available for the distribution of the number of system resources and the allocation method within the guaranteed amounts of system resources for individual virtual network segments.

Interactions between nascent proteins and the ribosome surface inhibit co-translational folding

Most proteins begin to fold during biosynthesis on the ribosome. It has been suggested that interactions between the emerging polypeptide and the ribosome surface might allow the ribosome itself to modulate co-translational folding. Here we combine protein engineering and NMR spectroscopy to characterize a series of interactions between the ribosome surface and unfolded nascent chains of the immunoglobulin-like FLN5 filamin domain. The strongest interactions are found for a C-terminal segment that is essential for folding, and we demonstrate quantitative agreement between the strength of this interaction and the energetics of the co-translational folding process itself. Mutations in this region that reduce the extent of binding result in a shift in the co-translational folding equilibrium towards the native state. Our results therefore demonstrate that a competition between folding and binding provides a simple, dynamic mechanism for the modulation of co-translational folding by the ribosome.