Khan, Amir R. and James, Susan and Quinn, Michelle K. and Altan, Irem and Charbonneau, Patrick and McManus, Jennifer J
(2019)
Temperature-Dependent Interactions Explain
Normal and Inverted Solubility in a yD-Crystallin
Mutant.
Biophysical Journal, 117.
pp. 930-937.
ISSN 0006-3495
Abstract
Protein crystal production is a major bottleneck in the structural characterization 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 proteinprotein contact formation in the crystal lattice is a major obstacle to predicting and optimizing crystallization. The relative scarcity
of sophisticated theoretical models that include sufficient detail to link collective behavior, captured in protein phase diagrams,
and molecular-level details, determined from high-resolution structural information, is a further barrier. Here, we present two
crystal structures for the P23T þ R36S mutant of gD-crystallin, each with opposite solubility behavior: 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 stabilize 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 a productive strategy for the rationalization of
protein crystallization.
| Item Type: |
Article
|
| Keywords: |
Temperature-Dependent Interactions;
Normal solubility; Inverted Solubility; yD-Crystallin
Mutant; |
| Academic Unit: |
Faculty of Science and Engineering > Chemistry |
| Item ID: |
13459 |
| Identification Number: |
https://doi.org/10.1016/j.bpj.2019.07.019 |
| Depositing User: |
IR Editor
|
| Date Deposited: |
28 Oct 2020 10:58 |
| Journal or Publication Title: |
Biophysical Journal |
| Publisher: |
Cell Press |
| Refereed: |
Yes |
| URI: |
|
| Use Licence: |
This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available
here |
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