While the majority of proteins with available structures are able to fold independently and mediate interactions only after acquiring their folded state, a subset of the known protein complexes contains protein chains that are intrinsically disordered in isolation. The Mutual Folding Induced by Binding (MFIB) database collects and classifies protein complexes, wherein all constituent protein chains would be unstable/disordered in isolation but fold into a well-defined 3D complex structure upon binding. This phenomenon is often termed as cooperative folding and binding or mutual synergistic folding (MSF). Here we present a major update to the database: we collected and annotated hundreds of new protein complexes fulfilling the criteria of MSF, leading to an almost six-fold increase in the size of the database. Many novel features have also been introduced, such as clustering of the complexes based on structural similarity and domain types, assigning different evidence levels to each entry and adding the evidence coverage label that allowed us to include complexes of multi(sub)domain monomers with partial MSF. The MFIB 2.0 database is available at https://mfib.pbrg.hu.
Introduction: Methyltransferase-like protein 3 (METTL3), in complex with METTL14, is the key 'writer' protein for RNA mA methylation, accounting for almost all mRNA mA modifications. Recent studies reveal that METTL3 is implicated in the development and progression of various types of cancers. Targeting METTL3 with small molecule inhibitors represents a promising therapeutic strategy for cancer.
Low-frequency non-syndromic hearing loss (LFNSHL) is a rare auditory disorder affecting frequencies ≤ 2000 Hz. To elucidate its genetic basis, we conducted whole-exome sequencing on nine Chinese families (31 affected individuals) with LFNSHL. Four heterozygous pathogenic variants, including two novel variants, were identified in common LFNSHL-related genes (WFS1, DIAPH1) and less common genes (TNC, EYA4), achieving a 44% genetic diagnosis rate.
Antimicrobial resistance is a significant cause of mortality globally due to infections, a trend that is expected to continue to rise. As existing treatments fail and new drug discovery slows, the urgency to develop novel antimicrobial therapeutics grows stronger. One promising strategy involves targeting bacterial systems exclusive to pathogens, such as the transcription regulator protein GabR.
Background: Chronic hepatitis B virus (HBV) infection is a common but underdiagnosed and undertreated health condition and is the leading cause of hepatocellular carcinoma (HCC) worldwide. HBV (rated a Grade 1 carcinogen by the International Agency for Research on Cancer) drives the transformation of hepatocytes in multiple ways by inducing viral DNA integrations, genetic dysregulation, chromosomal translocations, chronic inflammation, and oncogenic pathways facilitated by some HBV proteins. Importantly, these mechanisms are active throughout all phases of HBV infection.
Throughout the COVID-19 pandemic, the emergence of new viral variants has challenged public health efforts, often evading antibody responses generated by infections and vaccinations. This immune escape has led to waves of breakthrough infections, raising questions about the efficacy and durability of immune protection. Here we focus on the impact of SARS-CoV-2 Delta and Omicron spike mutations on ACE-2 receptor binding, protein stability, and immune response evasion.
