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Understanding the structure and function of Plasmodium aminopeptidases to facilitate drug discovery
Curr Opin Struct Biol. 2023 Aug 30;82:102693. doi: 10.1016/j.sbi.2023.102693. Online ahead of print.ABSTRACTMalaria continues to be the most widespread parasitic disease affecting humans globally. As parasites develop drug resistance at an alarming pace, it has become crucial to identify novel drug targets. Over the last decade, the metalloaminopeptidases have gained importance as potential targets for new antimalarials. These enzymes are responsible for removing the N-terminal amino acids from proteins and peptides, and their restricted specificities suggest that many perform unique and essential roles within the malaria ...
Source: Current Opinion in Structural Biology - September 1, 2023 Category: Biology Authors: Mahta Mansouri Kajal Daware Chaille T Webb Sheena McGowan Source Type: research

Epigenetic inheritance and boundary maintenance at human centromeres
Curr Opin Struct Biol. 2023 Aug 30;82:102694. doi: 10.1016/j.sbi.2023.102694. Online ahead of print.ABSTRACTCentromeres are chromosomal regions that provide the foundation for microtubule attachment during chromosome segregation. Centromeres are epigenetically defined by nucleosomes containing the histone H3 variant centromere protein A (CENP-A) and, in many organisms, are surrounded by transcriptionally repressed pericentromeric chromatin marked by trimethylation of histone H3 lysine 9 (H3K9me3). Pericentromeric regions facilitate sister chromatid cohesion during mitosis, thereby supporting centromere function. Heterochro...
Source: Current Opinion in Structural Biology - September 1, 2023 Category: Biology Authors: Pragya Sidhwani Aaron F Straight Source Type: research

Nucleosomes unwrapped: Structural perspectives on transcription through chromatin
Curr Opin Struct Biol. 2023 Aug 24;82:102690. doi: 10.1016/j.sbi.2023.102690. Online ahead of print.ABSTRACTTranscription of most protein-coding genes requires the passage of RNA polymerase II through chromatin. Chromatin with its fundamental unit, the nucleosome, represents a barrier to transcription. How RNA polymerase II and associated factors traverse through nucleosomes and how chromatin architecture is maintained have remained largely enigmatic. Only recently, cryo-EM structures have visualized the transcription process through chromatin. These structures have elucidated how transcription initiation and transcription...
Source: Current Opinion in Structural Biology - August 26, 2023 Category: Biology Authors: Lucas Farnung Source Type: research

Holliday junction branch migration driven by AAA+ ATPase motors
Curr Opin Struct Biol. 2023 Aug 18;82:102650. doi: 10.1016/j.sbi.2023.102650. Online ahead of print.ABSTRACTHolliday junctions are key intermediate DNA structures during genetic recombination. One of the first Holliday junction-processing protein complexes to be discovered was the well conserved RuvAB branch migration complex present in bacteria that mediates an ATP-dependent movement of the Holliday junction (branch migration). Although the RuvAB complex served as a paradigm for the processing of the Holliday junction, due to technical limitations the detailed structure and underlying mechanism of the RuvAB branch migrati...
Source: Current Opinion in Structural Biology - August 21, 2023 Category: Biology Authors: Jiri Wald Thomas C Marlovits Source Type: research

Role of aberrant phase separation in pathological protein aggregation
Curr Opin Struct Biol. 2023 Aug 19;82:102678. doi: 10.1016/j.sbi.2023.102678. Online ahead of print.ABSTRACTNeurodegenerative diseases are associated with the pathological deposition of many different intrinsically disordered proteins or proteins with intrinsically disordered regions. Recent evidence suggests that these proteins can undergo liquid-liquid phase separation and also form membrane-less organelles in cells. Additionally, the biomolecular condensates formed by these proteins may undergo liquid-to-solid phase transition thereby maturating to amyloid fibrils, oligomeric species, or amorphous aggregates and contrib...
Source: Current Opinion in Structural Biology - August 21, 2023 Category: Biology Authors: Pijush Chakraborty Markus Zweckstetter Source Type: research

Insights in bacterial genome folding
Curr Opin Struct Biol. 2023 Aug 19;82:102679. doi: 10.1016/j.sbi.2023.102679. Online ahead of print.ABSTRACTChromosomes in all domains of life are well-defined structural entities with complex hierarchical organization. The regulation of this hierarchical organization and its functional interplay with gene expression or other chromosome metabolic processes such as repair, replication, or segregation is actively investigated in a variety of species, including prokaryotes. Bacterial chromosomes are typically gene-dense with few non-coding sequences and are organized into the nucleoid, a membrane-less compartment composed of ...
Source: Current Opinion in Structural Biology - August 21, 2023 Category: Biology Authors: Fares Osam Y áñez-Cuna Romain Koszul Source Type: research