Browsing by Subject "PROTEINS"

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    Allosteric modulation of nucleoporin assemblies by intrinsically disordered regions.
    (Science advances, 2019-11-27) Blus, Bartlomiej Jan; Koh, Junseock; Krolak, Aleksandra; Seo, Hyuk-Soo; Coutavas, Elias; Blobel, Günter
    Intrinsically disordered regions (IDRs) of proteins are implicated in key macromolecular interactions. However, the molecular forces underlying IDR function within multicomponent assemblies remain elusive. By combining thermodynamic and structural data, we have discovered an allostery-based mechanism regulating the soluble core region of the nuclear pore complex (NPC) composed of nucleoporins Nup53, Nic96, and Nup157. We have identified distinct IDRs in Nup53 that are functionally coupled when binding to partner nucleoporins and karyopherins (Kaps) involved in NPC assembly and nucleocytoplasmic transport. We show that the Nup53·Kap121 complex forms an ensemble of structures that destabilize Nup53 hub interactions. Our study provides a molecular framework for understanding how disordered and folded domains communicate within macromolecular complexes.
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    Using Schematic Models to Understand the Microscopic Basis for Inverted Solubility in γD-Crystallin.
    (The journal of physical chemistry. B, 2019-11) Altan, Irem; Khan, Amir R; James, Susan; Quinn, Michelle K; McManus, Jennifer J; Charbonneau, Patrick
    Inverted solubility-melting a crystal by cooling-is observed in a handful of proteins, such as carbomonoxy hemoglobin C and γD-crystallin. In human γD-crystallin, the phenomenon is associated with the mutation of the 23rd residue, a proline, to a threonine, serine, or valine. One proposed microscopic mechanism entails an increase in surface hydrophobicity upon mutagenesis. Recent crystal structures of a double mutant that includes the P23T mutation allow for a more careful investigation of this proposal. Here, we first measure the surface hydrophobicity of various mutant structures of γD-crystallin and discern no notable increase in hydrophobicity upon mutating the 23rd residue. We then investigate the solubility inversion regime with a schematic patchy particle model that includes one of three variants of temperature-dependent patch energies: two of the hydrophobic effect, and one of a more generic nature. We conclude that, while solubility inversion due to the hydrophobic effect may be possible, microscopic evidence to support it in γD-crystallin is weak. More generally, we find that solubility inversion requires a fine balance between patch strengths and their temperature-dependent component, which may explain why inverted solubility is not commonly observed in proteins. We also find that the temperature-dependent interaction has only a negligible impact on liquid-liquid phase boundaries of γD-crystallin, in line with previous experimental observations.