During cell division, interactions between microtubules and chromosomes are mediated by the kinetochore, a proteinaceous structure located at the primary constriction of chromosomes. In addition to the centromere histone centromere protein A (CENP-A), 15 other members of the constitutive centromere associated network (CCAN) participate in the formation of a chromatin-associated scaffold that supports kinetochore structure. We performed a targeted screen analyzing unfolded centrochromatin from CENP-depleted chromosomes. Our results revealed that CENP-C and CENP-S are critical for the stable folding of mitotic kinetochore chromatin. Multipeak fitting algorithms revealed the presence of an organized pattern of centrochromatin packing consistent with arrangement of CENP-A-containing nucleosomes into up to five chromatin "subunits"-each containing roughly 20-30 nucleosomes. These subunits could be either layers of a boustrophedon or small loops of centromeric chromatin.
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http://dx.doi.org/10.1073/pnas.1614145114 | DOI Listing |
J Neurosci
January 2025
Department of Electrical and Computer Engineering, University of Maryland, College Park, MD, 20742
When we listen to speech, our brain's neurophysiological responses "track" its acoustic features, but it is less well understood how these auditory responses are enhanced by linguistic content. Here, we recorded magnetoencephalography (MEG) responses while subjects of both sexes listened to four types of continuous-speech-like passages: speech-envelope modulated noise, English-like non-words, scrambled words, and a narrative passage. Temporal response function (TRF) analysis provides strong neural evidence for the emergent features of speech processing in cortex, from acoustics to higher-level linguistics, as incremental steps in neural speech processing.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 636921, Singapore.
Enzyme-catalyzed protein modifications have become invaluable in diverse applications, outperforming chemical methods in terms of precision, conjugation efficiency, and biological compatibility. Despite significant advances in ligases, such as sortase A and OaAEP1, their use in heterogeneous biological environments remains constrained by limited target sequence specificity. In 2021, Lupas' group introduced Connectase, a family of repurposed archaeal proteases for protein ligations, but its low processivity and lack of structural information have impeded further engineering for practical biological and biophysical applications.
View Article and Find Full Text PDFbioRxiv
June 2024
Department of Cell Biology, Yale University School of Medicine, New Haven, CT, USA.
Life Sci Alliance
September 2024
Division of Genetics and Cell Biology, Vita-Salute San Raffaele University, Milan, Italy
The unfolded protein response can switch from a pro-survival to a maladaptive, pro-apoptotic mode. During ER stress, IRE1α sensors dimerize, become phosphorylated, and activate XBP1 splicing, increasing folding capacity in the ER protein factory. The steps that turn on the IRE1α endonuclease activity against endogenous mRNAs during maladaptive ER stress are still unknown.
View Article and Find Full Text PDFChem Sci
June 2024
Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, Xi'an Key Laboratory of Polymeric Soft Matter, International Joint Research Center on Functional Fiber and Soft Smart Textile, School of Chemistry and Chemical Engineering, Shaanxi Normal University Xi'an 710119 China
The amyloid states of proteins are implicated in several neurodegenerative diseases and bioadhesion processes. However, the classical amyloid fibrillization mechanism fails to adequately explain the formation of polymorphic aggregates and their adhesion to various surfaces. Herein, we report a non-fibril amyloid aggregation pathway, with disulfide-bond-reduced lysozyme (R-Lyz) as a model protein under quasi-physiological conditions.
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