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| Main Authors: | , , , , |
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| Format: | Artículo Open Access |
| Published: |
Wiley
2026
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| Subjects: | |
| Online Access: | https://onlinelibrary.wiley.com/doi/10.1002/pro.70608 |
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Table of Contents:
- Functionally related internal fluctuations in human ileal bile acid‐binding protein by high pressure nuclear magnetic resonance Tamara Teski Bence Balterer Gergő Horváth Gábor Turczel Orsolya Toke Protein Science Abstract Hidden protein states with partially unfolded regions can have a functional relevance and may also contribute to an uncontrolled self‐association of proteins leading to pathological conditions. Human ileal bile acid‐binding protein (hI‐BABP), a member of the family of intracellular lipid‐binding proteins (iLBPs), plays a key role in the transcellular trafficking and metabolic targeting of bile salts. Disorder–order transitions and sparsely populated hidden states in hI‐BABP are thought to be key elements of ligand recognition, with implications for bile salt recycling and bile salt‐mediated signaling events. To improve our understanding of the structural determinants of hI‐BABP stability, high pressure NMR was used to probe local packing interactions and characterize the folding/unfolding process. Heterogeneity in pressure response, revealed by residue‐specific analysis of chemical shift and intensity changes, indicates a deviation from two‐state unfolding. Four specific protein regions such as the N‐terminal β‐strand, the helical cap, a hydrophobic cluster at the bottom of the β‐barrel, and segments of the HIJ‐region have been found to exhibit a pressure response differing significantly from the rest of the protein. Our analysis further shows that a low‐populated higher‐energy state, inferred by NMR relaxation dispersion measurements, becomes less distinct from the ground state at high pressure, corroborating the hypothesis that conformational exchange between a closed and a more open EFGH‐region, which mediates ligand entry, is related to a partial unfolding of the protein. A pathway of destabilization induced by high hydrostatic pressure is proposed and discussed in relation to the response of iLBPs to other stress conditions. 10.1002/pro.70608 http://creativecommons.org/licenses/by/4.0/