6ETA

Crystal Structure of Human Gamma-D crystallin Mutant P23T+R36S at Room Temperature

Summary for 6ETA

• Entry DOI: 10.2210/pdb6eta/pdb
• Descriptor: Gamma-crystallin D (2 entities in total)
• Functional Keywords: age-related cateract eye lens protein structural protein, structural protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 41400.08

Authors

James, S.,McManus, J.,Khan, A.R. (deposition date: 2017-10-25, 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

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: 31422822
DOI: 10.1016/j.bpj.2019.07.019

Experimental method

X-RAY DIFFRACTION (2.198 Å)