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Temperature-dependent non-covalent protein-protein interactions explain normal and inverted solubility in a mutant of human gamma D-crystallin

dc.contributor.author Charbonneau, Patrick
dc.contributor.author Khan, Amir R
dc.contributor.author James, Susan
dc.contributor.author Quinn, Michelle K
dc.contributor.author Altan, Irem
dc.contributor.author McManus, Jennifer J
dc.date.accessioned 2019-02-05T01:55:02Z
dc.date.available 2019-02-05T01:55:02Z
dc.identifier.uri https://hdl.handle.net/10161/18058
dc.description.abstract Protein crystal production is a major bottleneck for the structural characterisation of proteins. To advance beyond large-scale screening, rational strategies for protein crystallization are crucial. Understanding how chemical anisotropy (or patchiness) of the protein surface due to the variety of amino acid side chains in contact with solvent, contributes to protein protein contact formation in the crystal lattice is a major obstacle to predicting and optimising crystallization. The relative scarcity of sophisticated theoretical models that include sufficient detail to link collective behaviour, captured in protein phase diagrams, and molecular level details, determined from high-resolution structural information is a further barrier. Here we present two crystals structures for the P23TR36S mutant of gamma D-crystallin, each with opposite solubility behaviour, one melts when heated, the other when cooled. When combined with the protein phase diagram and a tailored patchy particle model we show that a single temperature dependent interaction is sufficient to stabilise the inverted solubility crystal. This contact, at the P23T substitution site, relates to a genetic cataract and reveals at a molecular level, the origin of the lowered and retrograde solubility of the protein. Our results show that the approach employed here may present an alternative strategy for the rationalization of protein crystallization.
dc.subject q-bio.BM
dc.subject q-bio.BM
dc.subject cond-mat.soft
dc.subject physics.bio-ph
dc.title Temperature-dependent non-covalent protein-protein interactions explain normal and inverted solubility in a mutant of human gamma D-crystallin
dc.type Journal article
dc.date.updated 2019-02-05T01:55:00Z
pubs.organisational-group Trinity College of Arts & Sciences
pubs.organisational-group Duke
pubs.organisational-group Chemistry
pubs.organisational-group Physics
duke.contributor.orcid Charbonneau, Patrick|0000-0001-7174-0821


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