6ETC
Crystal Structure of Human gamma-D-crystallin Mutant P23T+R36S at 1.2 Angstroms Resolution
Summary for 6ETC
| Entry DOI | 10.2210/pdb6etc/pdb |
| Related | 6eta |
| Descriptor | Gamma-crystallin D (2 entities in total) |
| Functional Keywords | human eye lens protein age-related cataract structural protein, structural protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 20700.04 |
| Authors | Khan, A.R.,McManus, J. (deposition date: 2017-10-26, release date: 2018-11-07, Last modification date: 2024-01-17) |
| Primary citation | Khan, A.R.,James, S.,Quinn, M.K.,Altan, I.,Charbonneau, P.,McManus, J.J. Temperature-Dependent Interactions Explain Normal and Inverted Solubility in a gamma D-Crystallin Mutant. Biophys.J., 117:930-937, 2019 Cited by PubMed 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 protein-protein 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 + R36S mutant of γD-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. PubMed: 31422822DOI: 10.1016/j.bpj.2019.07.019 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.197 Å) |
Structure validation
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