Summary for 7RJ0
| Entry DOI | 10.2210/pdb7rj0/pdb |
| Descriptor | Gamma-crystallin S (2 entities in total) |
| Functional Keywords | octamer, domain-swap, oxidation, disorder, protein binding, structural protein |
| Biological source | Mus musculus (Mouse) |
| Total number of polymer chains | 4 |
| Total formula weight | 83679.52 |
| Authors | Sagar, V. (deposition date: 2021-07-20, release date: 2022-04-13, Last modification date: 2024-11-06) |
| Primary citation | Sagar, V.,Wistow, G. Acquired Disorder and Asymmetry in a Domain-Swapped Model for gamma-Crystallin Aggregation. J.Mol.Biol., 434:167559-167559, 2022 Cited by PubMed Abstract: Misfolding and aggregation of proteins occur in many pathological states. Because of the inherent disorder involved, these processes are difficult to study. We attempted to capture aggregation intermediates of γS-crystallin, a highly stable, internally symmetrical monomeric protein, by crystallization under mildly acidic and oxidizing conditions. Here we describe novel oligomerization through strained domain-swapping and partial intermolecular disulfide formation. This forms an octamer built from asymmetric tetramers, each of which comprises an asymmetric pair of twisted, domain-swapped dimers. Each tetramer shows patterns of acquired disorder among subunits, ranging from local loss of secondary structure to regions of intrinsic disorder. The octamer ring is tied together by partial intermolecular disulfide bonds, which may contribute to strain and disorder in the octamer. Oligomerization in this structure is self-limited by the distorted octamer ring. In a more heterogeneous environment, the disordered regions could serve as seeds for cascading interactions with other proteins. Indeed, solubilized protein from crystals retain many features observed in the crystal and are prone to further oligomerization and precipitation. This structure illustrates modes of loss of organized structure and aggregation that are relevant for cataract and for other disorders involving deposition of formerly well-folded proteins. PubMed: 35341744DOI: 10.1016/j.jmb.2022.167559 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.919 Å) |
Structure validation
Download full validation report
