Proprietary alpha-amylase inhibitor formulation from white kidney bean (Phaseolus vulgaris L.) promotes weight and fat loss: a 12-week, double-blind, placebo-controlled, randomized trial.

White kidney bean (Phaseolus vulgaris L.) extracts can aid weight management by reducing calorie intake from complex carbohydrates through alpha-amylase inhibition. We examined the impact of a proprietary aqueous extract from whole dried white kidney beans standardized by its alpha-amylase inhibitor activity (Phase 2 white kidney bean extract (WKBE)) on weight management in subjects with overweight and moderate obesity. In a randomized, double-blind, placebo-controlled fashion, 81 participants completed the study and ingested either a high dose of Phase 2 (1000 mg, WKBE HIGH), a low dose (700 mg, WKBE LOW), or a matching placebo (microcrystalline cellulose, PLA) three times a day, 30 min before meals, for 12 weeks during a calorie restricted diet. In a dose-dependent manner, Phase 2 significantly reduced body weight, fat mass, BMI, waist, hip and in the WKBE HIGH group thigh circumference. Phase 2 is an effective and safe supplement aiding weight and fat loss. ClinicalTrials.gov identifier NCT02930668.

Structural characterization of Thogoto Virus nucleoprotein provides insights into viral RNA encapsidation and RNP assembly.

Orthomyxoviruses, such as influenza and thogotoviruses, are important human and animal pathogens. Their segmented viral RNA genomes are wrapped by viral nucleoproteins (NPs) into helical ribonucleoprotein complexes (RNPs). NP structures of several influenza viruses have been reported. However, there are still contradictory models of how orthomyxovirus RNPs are assembled. Here, we characterize the crystal structure of Thogoto virus (THOV) NP and found striking similarities to structures of influenza viral NPs, including a two-lobed domain architecture, a positively charged RNA-binding cleft, and a tail loop important for trimerization and viral transcription. A low-resolution cryo-electron tomography reconstruction of THOV RNPs elucidates a left-handed double helical assembly. By providing a model for RNP assembly of THOV, our study suggests conserved NP assembly and RNA encapsidation modes for thogoto- and influenza viruses.

Pathogenic mutations of human phosphorylation sites affect protein-protein interactions.

Despite their lack of a defined 3D structure, intrinsically disordered regions (IDRs) of proteins play important biological roles. Many IDRs contain short linear motifs (SLiMs) that mediate protein-protein interactions (PPIs), which can be regulated by post-translational modifications like phosphorylation. 20% of pathogenic missense mutations are found in IDRs, and understanding how such mutations affect PPIs is essential for unraveling disease mechanisms. Here, we employ peptide-based interaction proteomics to investigate 36 disease-associated mutations affecting phosphorylation sites. Our results unveil significant differences in interactomes between phosphorylated and non-phosphorylated peptides, often due to disrupted phosphorylation-dependent SLiMs. We focused on a mutation of a serine phosphorylation site in the transcription factor GATAD1, which causes dilated cardiomyopathy. We find that this phosphorylation site mediates interaction with 14-3-3 family proteins. Follow-up experiments reveal the structural basis of this interaction and suggest that 14-3-3 binding affects GATAD1 nucleocytoplasmic transport by masking a nuclear localisation signal. Our results demonstrate that pathogenic mutations of human phosphorylation sites can significantly impact protein-protein interactions, offering insights into potential molecular mechanisms underlying pathogenesis.