Deamidation of N76 in human γS-crystallin promotes dimer formation

Biochimica Et Biophysica Acta
Nicholas J RayJohn A Carver

Abstract

Cataract formation is often attributed to the build-up of post-translational modifications in the crystallin proteins of the eye lens. One such modification, the deamidation of N76 in human γS-crystallin to D76, is highly correlated with age-related cataract (Hooi et al. Invest. Ophthalmol. Vis. Sci. 53 (2012) 3554-3561). In the current work, this modification has been extensively characterised in vitro. Biophysical characterisation was performed on wild type and N76D γS-crystallins using turbidity measurements to monitor aggregation, intrinsic fluorescence and circular dichroism spectroscopy to determine the folded state and NMR spectroscopy for identifying local changes in structure. Protein mass was determined using SEC-MALLS and analytical ultracentrifugation methods. Relative to the wild type protein, deamidation at N76 in γS-crystallin causes an increase in the thermal stability and resistance to thermally induced aggregation alongside a decrease in stability to denaturants, a propensity to aggregate rapidly once destabilised and a tendency to form a dimer. We ascribe the apparent increase in thermal stability upon deamidation to the formation of dimer which prevents the unfolding of the inherently less stable monomer. De...Continue Reading

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Citations

Nov 1, 2015·Biochimica Et Biophysica Acta·K Krishna Sharma
Nov 18, 2017·Interface Focus·Karolina L ZapadkaSophie E Jackson
Jul 23, 2020·Protein Science : a Publication of the Protein Society·Calvin J VetterKirsten J Lampi
Jan 15, 2016·Mass Spectrometry Reviews·Piliang HaoSiu Kwan Sze
Jul 20, 2017·Scientific Reports·Bamaprasad DuttaSiu Kwan Sze
Jan 14, 2020·Protein Science : a Publication of the Protein Society·Takumi TakataNoriko Fujii
Aug 22, 2018·International Journal of Molecular Sciences·Yutaka Sadakane, Masahiro Kawahara
Jun 17, 2020·Methods : a Companion to Methods in Enzymology·Yujia Ying, Huilin Li
Feb 12, 2021·Chembiochem : a European Journal of Chemical Biology·Megan A RochaRachel W Martin
Dec 3, 2020·Structure·Alex J GusemanAngela M Gronenborn
Sep 30, 2020·International Journal of Molecular Sciences·Koichi KatoAkifumi Oda
Oct 28, 2019·Biochemistry·Kyle W RoskampRachel W Martin

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