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Structural characterization of the thermal unfolding pathway of human VEGFR1 D2 domain
Author(s) -
Diana Donatella,
Di Stasi Rossella,
GarcíaViñuales Sara,
De Rosa Lucia,
Isernia Carla,
Malgieri Gaetano,
Milardi Danilo,
D’Andrea Luca D.,
Fattorusso Roberto
Publication year - 2022
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.16246
Subject(s) - characterization (materials science) , domain (mathematical analysis) , thermal , materials science , nanotechnology , physics , thermodynamics , mathematics , mathematical analysis
Folding stability is a crucial feature of protein evolution and is essential for protein functions. Thus, the comprehension of protein folding mechanisms represents an important complement to protein structure and function, crucial to determine the structural basis of protein misfolding. In this context, thermal unfolding studies represent a useful tool to get a molecular description of the conformational transitions governing the folding/unfolding equilibrium of a given protein. Here, we report the thermal folding/unfolding pathway of VEGFR1D2, a member of the immunoglobulin superfamily by means of a high‐resolution thermodynamic approach that combines differential scanning calorimetry with atomic‐level unfolding monitored by NMR. We show how VEGFR1D2 folding is driven by an oxidatively induced disulfide pairing: the key event in the achievement of its functional structure is the formation of a small hydrophobic core that surrounds a disulfide bridge. Such a ‘folding nucleus’ induces the cooperative transition to the properly folded conformation supporting the hypothesis that a disulfide bond can act as a folding nucleus that eases the folding process.