Assessing the Structures and Interactions of γD-Crystallin Deamidation Variants

Overview

Journal Structure

Publisher Cell Press

Specialties Biochemistry
Biotechnology
Cell Biology
Molecular Biology

Date 2020 Dec 2

PMID 33264606

Citations 8

Authors

Alex J Guseman

Matthew J Whitley

Jeremy J Gonzalez

Nityam Rathi

Mikayla Ambarian

Angela M Gronenborn

Affiliations

Soon will be listed here.

Abstract

Cataracts involve the deposition of the crystallin proteins in the vertebrate eye lens, causing opacification and blindness. They are associated with either genetic mutation or protein damage that accumulates over the lifetime of the organism. Deamidation of Asn residues in several different crystallins has been observed and is frequently invoked as a cause of cataract. Here, we investigated the properties of Asp variants, deamidation products of γD-crystallin, by solution NMR, X-ray crystallography, and other biophysical techniques. No substantive structural or stability changes were noted for all seven Asn to Asp γD-crystallins. Importantly, no changes in diffusion interaction behavior could be detected. Our combined experimental results demonstrate that introduction of single Asp residues on the surface of γD-crystallin by deamidation is unlikely to be the driver of cataract formation in the eye lens.

Citing Articles

Cataract-prone variants of γD-crystallin populate a conformation with a partially unfolded N-terminal domain under native conditions.

Volz S, Malone J, Guseman A, Gronenborn A, Marqusee S Proc Natl Acad Sci U S A. 2025; 122(6):e2410860122.

PMID: 39899721 PMC: 11831119. DOI: 10.1073/pnas.2410860122.

Cumulative asparagine to aspartate deamidation fails to perturb γD-crystallin structure and stability.

Guseman A, Gonzalez J, Yang D, Gronenborn A Protein Sci. 2024; 33(8):e5120.

PMID: 39022918 PMC: 11255865. DOI: 10.1002/pro.5120.

An ultraviolet-driven rescue pathway for oxidative stress to eye lens protein human gamma-D crystallin.

Hill J, Nyathi Y, Horrell S, von Stetten D, Axford D, Owen R Commun Chem. 2024; 7(1):81.

PMID: 38600176 PMC: 11006947. DOI: 10.1038/s42004-024-01163-w.

Probing effects of site-specific aspartic acid isomerization on structure and stability of GB1 through chemical protein synthesis.

Heath S, Guseman A, Gronenborn A, Seth Horne W Protein Sci. 2023; 33(3):e4883.

PMID: 38143426 PMC: 10868458. DOI: 10.1002/pro.4883.

Insights into the biochemical and biophysical mechanisms mediating the longevity of the transparent optics of the eye lens.

Quinlan R, Clark J J Biol Chem. 2022; 298(11):102537.

PMID: 36174677 PMC: 9638808. DOI: 10.1016/j.jbc.2022.102537.

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