The X-ray Crystal Structure of Human γS-crystallin C-terminal Domain

Abstract

␥S-crystallin is a major human lens protein found in the outer region of the eye lens, where the refractive index is low. Because crystallins are not renewed they acquire post-translational modifications that may perturb stability and solubility. In common with other members of the ␤␥-crystallin superfamily, ␥S-crystallin comprises two similar ␤-sheet domains. The crystal structure of the C-terminal domain of human ␥S-crystallin has been solved at 2.4 Å resolution. The structure shows that in the in vitro expressed protein, the buried cysteines remain reduced. The backbone conformation of the "tyrosine corner" differs from that of other ␤␥-crystallins because of deviation from the consensus sequence. The two C-terminal domains in the asymmetric unit are organized about a slightly distorted 2-fold axis to form a dimer with similar geometry to full-length two-domain family members. Two glutamines found in lattice contacts may be important for short range interactions in the lens. An asparagine known to be deamidated in human cataract is located in a highly ordered structural region.

Structure and Substrate Specificity of a Eukaryotic Fucosidase from Fusarium graminearum

“…Consistent with this, calcium ions were not found in the crystal structures of FgFCO1 nor did adding calcium shift the Tm of the enzyme ([Ca 2ϩ ] between 5 M and 1 mM; data not shown). The absence of a calcium binding motif was also reported in the human eye ␥S-crystallin and many other ␤␥-crystallins (69,70).…”

“…0.95 Å of 81 residues, sequence identity 24%) (69), and also the C-terminal domain of human eye ␥S-crystallin (PDB code 1HA4, C-␣ r.m.s.d. 1.88 Å of 77 residues, sequence identity 25%) (70) (Fig. 6b).…”

Age‐dependent deamidation of glutamine residues in human γS crystallin: Deamidation and unstructured regions

“…This addition of a negative charge could interrupt the short-range interactions of human cS crystallin that have been previously observed. 30 Recent data…”

Gamma crystallins of the human eye lens

“…(Also, the crystal structure of the Cterminal domain of human γS-crystallin has been determined [18].) The molecule is seen to pack in a highly symmetric manner, with each of the two domains as tightly packed β-sheet sandwiches made of Greek key motifs.…”