Peptidoglycan is a widespread bacterial PAMP molecule and a powerful initiator of innate immune responses. It consists of repeating units of MDP, which as a monomer is only weakly immunostimulatory. Here, MDP-coupled dendrimers were prepared and investigated for stimulation of pig blood mononuclear cells. Compared to monomeric MDP, MDP-dendrimers induced a markedly enhanced production of IL-12 p40, IL-1β and IL-6 and completely down-regulated surface expression of B7 and MHC class II. These results suggest a possible novel strategy based on controlled multimerization of minimal PAMP motifs on dendrimers for preparing molecularly defined immunostimulators with predictable bioactivities.
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http://dx.doi.org/10.1002/mabi.201100105 | DOI Listing |
J Prev Alzheimers Dis
January 2025
CenExel iResearch, Atlanta, GA, USA.
Background: Soluble species of multimeric amyloid-beta including globular amyloid-beta oligomers (AβOs) and linear amyloid-beta protofibrils are toxic to neurons. Sabirnetug (ACU193) is a humanized monoclonal antibody, raised against globular species of soluble AβO, that has over 650-fold greater binding affinity for AβOs over monomers and appears to have relatively little binding to amyloid plaque.
Objectives: To assess safety, pharmacokinetics, and exploratory measures including target engagement, biomarker effects, and clinical efficacy of sabirnetug in participants with early symptomatic Alzheimer's disease (AD; defined as mild cognitive impairment and mild dementia due to AD).
Nat Commun
January 2025
Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), Heidelberg, Germany.
The γ-tubulin ring complex (γ-TuRC) is a structural template for controlled nucleation of microtubules from α/β-tubulin heterodimers. At the cytoplasmic side of the yeast spindle pole body, the CM1-containing receptor protein Spc72 promotes γ-TuRC assembly from seven γ-tubulin small complexes (γ-TuSCs) and recruits the microtubule polymerase Stu2, yet their molecular interplay remains unclear. Here, we determine the cryo-EM structure of the Candida albicans cytoplasmic nucleation unit at 3.
View Article and Find Full Text PDFProtein Sci
January 2025
Department of Biotechnology, Bhupat & Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, India.
H-NS, a nucleoid-associated protein (NAP) from enterobacteria, regulates gene expression by dynamically transducing environmental cues to conformational assembly and DNA binding. In this work, we show that H-NS from Escherichia coli, which can assemble into octameric and tetrameric oligomerization states, forms spontaneous micron-sized liquid-like condensates with DNA at sub-physiological concentrations in vitro. The heterotypic condensates are metastable at 298 K, partially solubilizing with time, while still retaining their liquid-like properties.
View Article and Find Full Text PDFBiochemistry
December 2024
College of Future Technology, Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China.
Deoxyribonucleic acid (DNA) nanomachines have been widely exploited in enzyme activity regulation, protein crystallization, protein assembly, and control of the protein-protein interaction (PPI). Yet, the fundamental biophysical framework of DNA nanomachines in the case of regulating protein-protein interactions remains elusive. Here, we established a DNA nanospring-mCherry model with mCherry homodimers of different .
View Article and Find Full Text PDFProc Natl Acad Sci U S A
November 2024
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA.
Collagens are the foundational component of diverse tissues, including skin, bone, cartilage, and basement membranes, and are the most abundant protein class in animals. The fibrillar collagens are large, complex, multidomain proteins, all containing the characteristic triple helix motif. The most prevalent collagens are heterotrimeric, meaning that cells express at least two distinctive procollagen polypeptides that must assemble into specific heterotrimer compositions.
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