Year: 2026
Type: article
Abstract: The central role of YB-1 in messenger ribonucleoprotein particle (mRNP) metabolism and stress-granule biology highlights the importance of defining the determinants of its self-assembly. YB-1 fibrillogenesis has been attributed primarily to the cold shock domain (CSD). Here, we show that the YB-1 fragment spanning residues 1–129 (AP–CSD) form amyloid fibrils under near-physiological ionic strength (0.12–0.15 M KCl). Fibrillization proceeds without a pronounced exponential growth phase and increases approximately linearly over 45–50 h. Far-UV circular dichroism (CD) and attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) indicate no substantial change in overall secondary-structure content during aggregation. In parallel, 1H nuclear magnetic resonance (NMR) spectroscopy reveals the depletion of soluble species, and oriented fiber X-ray diffraction displays the hallmark cross-β reflections at approximately 4.7 Å and 10 Å. The prolonged formation time implies an activation barrier that is unlikely to require global refolding. Instead, it may reflect early association events such as dimerization or other local rearrangements required for primary nucleation, followed by consolidation into stable intermolecular contacts. Aggregation that preserves a largely native-like fold while establishing cross-β order may reduce recognition by cellular quality-control systems that preferentially target globally unfolded or strongly destabilized states. This provides a plausible framework for how YB-1 derived assemblies could persist under stress and during age-associated proteostasis decline.
DOI: 10.3390/ijms27083553
Authors: Maria A. Timchenko, Oxana V. Galzitskaya, Alexander V. Chulkov, Ilya V. Likhachev, Anna V. Glyakina, Maxim V. Molchanov, Nikolay V. Molochkov, Nikita V. Penkov, Liya G. Bobyleva, Vitalii A. Balobanov, Alexander Ye. Yegorov, Sergey G. Guryanov, Alexey D. Nikulin, Dmitry N. Lyabin, Ivan M. Vikhlyantsev, Alexander G. Bobylev
Institutions: Russian Academy of Sciences, Institute of Theoretical and Experimental Biophysics, Gamalei Institute of Epidemiology and Microbiology, Institute of Protein Research, Mari State University, Institute of Mathematical Problems of Biology, Keldysh Institute of Applied Mathematics, Institute of Cell Biophysics, Sirius University of Science and Technology
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,499
OpenAlex ID: W7154611182