Exome Sequencing of Fetuses With Intracranial Hemorrhage Unravels Novel Causative Genes and an Extreme Genetic Heterogeneity.

Objective: Fetal intracranial hemorrhage (FICH) is a rare and potentially deleterious condition. Fetal alloimmune thrombocytopenia and pathogenic variations in COL4A1/A2 genes are well-recognized causes of FICH. However, pathogenic COL4A1/A2 variations are identified in only 20% of fetuses referred for FICH after excluding other known causes, leaving the majority unexplained and making genetic counseling difficult.

Lysosomal damage due to cholesterol accumulation triggers immunogenic cell death.

Cholesterol serves as a vital lipid that regulates numerous physiological processes. Nonetheless, its role in regulating cell death processes remains incompletely understood. In this study, we investigated the role of cholesterol trafficking in immunogenic cell death.

Special Issue: "Molecular Dynamics Simulations and Structural Analysis of Protein Domains".

The 3D protein structure is the basis for all their biological functions [...

AlphaFold2 for Protein Structure Prediction: Best Practices and Critical Analyses.

AlphaFold2 (AF2) has emerged in recent years as a groundbreaking innovation that has revolutionized several scientific fields, in particular structural biology, drug design, and the elucidation of disease mechanisms. Many scientists now use AF2 on a daily basis, including non-specialist users. This chapter is aimed at the latter.

Molecular dynamics of the human RhD and RhAG blood group proteins.

Blood group antigens of the RH system (formerly known as "Rhesus") play an important role in transfusion medicine because of the severe haemolytic consequences of antibodies to these antigens. No crystal structure is available for RhD proteins with its partner RhAG, and the precise stoichiometry of the trimer complex remains unknown. To analyse their structural properties, the trimers formed by RhD and/or RhAG subunits were generated by protein modelling and molecular dynamics simulations were performed.

HumanLectome, an update of UniLectin for the annotation and prediction of human lectins.

The UniLectin portal (https://unilectin.unige.ch/) was designed in 2019 with the goal of centralising curated and predicted data on carbohydrate-binding proteins known as lectins.

Evaluation of the Potential Impact of In Silico Humanization on VH Dynamics.

Camelids have the peculiarity of having classical antibodies composed of heavy and light chains as well as single-chain antibodies. They have lost their light chains and one heavy-chain domain. This evolutionary feature means that their terminal heavy-chain domain, VH, called VH here, has no partner and forms an independent domain.

Structural Space of the Duffy Antigen/Receptor for Chemokines' Intrinsically Disordered Ectodomain 1 Explored by Temperature Replica-Exchange Molecular Dynamics Simulations.

malaria affects 14 million people each year. Its invasion requires interactions between the parasitic Duffy-binding protein (DBP) and the N-terminal extracellular domain (ECD1) of the host's Duffy antigen/receptor for chemokines (DARC). ECD1 is highly flexible and intrinsically disordered, therefore it can adopt different conformations.

Special Issue: New Advances in Bioinformatics and Biomedical Engineering Using Machine Learning Techniques, IWBBIO-2022.

Bioinformatics is revolutionizing Biomedicine in the way we treat and diagnose pathologies related to biological manifestations resulting from variations or mutations of our DNA [...

A perspective on the sharing of docking data.

Computational approaches are nowadays largely applied in drug discovery projects. Among these, molecular docking is the most used for hit identification against a drug target protein. However, many scientists in the field shed light on the lack of availability and reproducibility of the data obtained from such studies to the whole community.

Structural and Dynamic Differences between Calreticulin Mutants Associated with Essential Thrombocythemia.

Essential thrombocythemia (ET) is a blood cancer. ET is characterized by an overproduction of platelets that can lead to thrombosis formation. Platelet overproduction occurs in megakaryocytes through a signaling pathway that could involve JAK2, MPL, or CALR proteins.

General Trends of the Antibody VHs Domain Dynamics.

Conformational flexibility plays an essential role in antibodies' functional and structural stability. They facilitate and determine the strength of antigen-antibody interactions. Camelidae express an interesting subtype of single-chain antibody, named Heavy Chain only Antibody.

Quality assessment of VH models.

Heavy Chain Only Antibodies are specific to Camelid species. Despite the lack of the light chain variable domain, their heavy chain variable domain (VH) domain, named VH or nanobody, has promising potential applications in research and therapeutic fields. The structural study of VH is therefore of great interest.

A novel high-prevalence antigen in the Lutheran system, LUGA (LU24), and an updated, full-length 3D BCAM model.

Background: The basal cell adhesion molecule (BCAM) carries the antigens of the Lutheran (LU, ISBT005) system. We report a novel Lutheran antigen and propose an updated, full-length 3D model of BCAM.

Study Design And Methods: Red blood cell testing, antibody identification, and BCAM genomic DNA sequencing were done by standard methods.

Conformational and binding mode assessment of the human IL-3 recognition by its alpha receptor.

Protein-protein interactions (PPIs) are attractive targets as they are critical in a variety of biological processes and pathologies. As an illustration, the interleukin 3 (IL-3) and its α subunit receptor (IL-3Rα) are two proteins belonging to the cytokine or receptor βc family and are involved in several disorders like inflammatory diseases or hematological malignancies. This PPI exhibits a low binding affinity and a complex formed by a mutant form of IL-3 (superkine) and IL-3Rα have emerged from the literature, with an increase of the affinity.

An agnostic analysis of the human AlphaFold2 proteome using local protein conformations.

Knowledge of the 3D structure of proteins is a valuable asset for understanding their precise biological mechanisms. However, the cost of production of 3D structures and experimental difficulties limit their obtaining. The proposal of 3D structural models is consequently an appealing alternative.

Two new Scianna variants causing loss of high prevalence antigens: ERMAP model and 3D analysis of the antigens.

Background: Scianna (Sc) antigens, seven high and two of low prevalence, are expressed on erythrocyte membrane-associated protein (ERMAP). We investigated SC (ERMAP) in individuals who made antibodies to high prevalence Scianna antigens, and propose a 3D model for ERMAP to precisely localize the residues associated with the known antigens.

Methods: Serological testing and DNA sequencing was performed by standard methods.

A Perspective on the (Rise and Fall of) Protein β-Turns.

The β-turn is the third defined secondary structure after the α-helix and the β-sheet. The β-turns were described more than 50 years ago and account for more than 20% of protein residues. Nonetheless, they are often overlooked or even misunderstood.

SWORD2: hierarchical analysis of protein 3D structures.

Understanding the functions and origins of proteins requires splitting these macromolecules into fragments that could be independent in terms of folding, activity, or evolution. For that purpose, structural domains are the typical level of analysis, but shorter segments, such as subdomains and supersecondary structures, are insightful as well. Here, we propose SWORD2, a web server for exploring how an input protein structure may be decomposed into 'Protein Units' that can be hierarchically assembled to delimit structural domains.

VH Structural Modelling Approaches: A Critical Review.

VH, i.e., VH domains of camelid single-chain antibodies, are very promising therapeutic agents due to their significant physicochemical advantages compared to classical mammalian antibodies.

Prediction of structural alphabet protein blocks using data mining.

3D protein structures determine proteins' biological functions. The 3D structure of the protein backbone can be approximated using the prototypes of local protein conformations. Sets of these prototypes are called structural alphabets (SAs).