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Precise Identification of Native Peptides with Posttranslational Proline Hydroxylation by Nanopore.
Angew Chem Int Ed Engl
January 2025
Nanjing University, School of Chemistry and Chemical Engineering, No. 163 Xianlin Road, 210023, Nanjing, CHINA.
Hydroxylation, an extensive post-translational modification on proline, is critical for the modulation of protein structures, further dominating their functions in life systems. However, current mass spectrometry-based identification, could hardly distinguish hydroxylation from neighboring oxidation due to the same mass shifts, as well as challenges posed by low abundance and exogenous oxidation during sample preparation. To address these, an engineered nanopore was designed, capable of discriminating single hydroxyl group, to achieve the identification of proline hydroxylation on individual native peptides directly in the mixture.
View Article and Find Full Text PDFCaML: Chemistry-informed machine learning explains mutual changes between protein conformations and calcium ions in calcium-binding proteins using structural and topological features.
Protein Sci
February 2025
Department of Physics, University of Washington, Seattle, Washington, USA.
Proteins' flexibility is a feature in communicating changes in cell signaling instigated by binding with secondary messengers, such as calcium ions, associated with the coordination of muscle contraction, neurotransmitter release, and gene expression. When binding with the disordered parts of a protein, calcium ions must balance their charge states with the shape of calcium-binding proteins and their versatile pool of partners depending on the circumstances they transmit. Accurately determining the ionic charges of those ions is essential for understanding their role in such processes.
View Article and Find Full Text PDFEngineered protein G variants for multifunctional antibody-based assemblies.
Protein Sci
February 2025
Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, Illinois, USA.
We have developed a portfolio of antibody-based modules that can be prefabricated as standalone units and snapped together in plug-and-play fashion to create uniquely powerful multifunctional assemblies. The basic building blocks are derived from multiple pairs of native and modified Fab scaffolds and protein G (PG) variants engineered by phage display to introduce high pair-wise specificity. The variety of possible Fab-PG pairings provides a highly orthogonal system that can be exploited to perform challenging cell biology operations in a straightforward manner.
View Article and Find Full Text PDFElevated LIF and JAK-STAT activation drive severe COVID-19 in myeloma patients receiving the BCMA-CD3 bispecific antibody Elranatamab.
J Transl Med
January 2025
Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Beijing, 100730, China.
Background: Immunotherapy is a significant risk factor for severe COVID-19 in multiple myeloma (MM) patients. Understanding how immunotherapies lead to severe COVID-19 is crucial for improving patient outcomes.
Methods: Human protein microarrays were used to examine the expression of 440 protein molecules in MM patients treated with bispecific T-cell engagers (BiTe) (n = 9), anti-CD38 monoclonal antibodies (mAbs) (n = 10), and proteasome inhibitor (PI)-based regimens (n = 10).
NLRP7 maintains the genomic stability during early human embryogenesis via mediating alternative splicing.
Commun Biol
January 2025
Department of Neurosurgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
Genomic instability is the main cause of abnormal embryo development and abortion. NLRP7 dysfunctions affect embryonic development and lead to Hydatidiform Moles, but the underlying mechanisms remain largely elusive. Here, we show that NLRP7 knockout affects the genetic stability, resulting in increased DNA damage in both human embryonic stem cells and blastoids, making embryonic cells in blastoids more susceptible to apoptosis.
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