# Acylation of Lens Proteins

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2021 · $415,209

## Abstract

N-acylation of cytosolic proteins is a common occurrence in tissues, and it regulates protein structure and
function. The major N-acylation types in cells are acetylation, propionylation, succinylation and malonylation,
which are initiated by the enzymatic or non-enzymatic transfer of acetyl CoA, propionyl CoA, succinyl CoA
and malonyl CoA to lysine residues, respectively. Lens proteins are long lived with little or no turnover, and
thus, post-translational modifications (PTMs) accumulate with age. The lack of enzymatically active proteins,
particularly in the core of the lens, prohibits the reversal of PTMs. Thus, if deacylases are weak in the lens,
acylation is mostly a one-way reaction that leads to permanent modifications of lens proteins, which appears
to be the case (based on our preliminary data). The effects of acylation on lens proteins remain largely
unknown. As shown in our previous study, the acetylation makes α-crystallin a better chaperone. In addition,
our preliminary data show that lens proteins are also propionylated, succinylated and malonylated and that
acetylation and succinylation increase the thermal stability and solubility of the proteins. Thus, we
hypothesize that acylation of lens proteins is a beneficial PTM that helps maintain the chaperone activity of α-
crystallin as well as the stability and solubility of lens proteins during aging. We will test this hypothesis in
three aims. In Aim 1, we will determine the major acylation sites in human lens α-crystallin by mass
spectrometric analyses and determine the effect of age on these modifications. In Aim 2, we will determine
effects of acylation on the structure and function of α-crystallin. In Aim 3, we will evaluate the effects of
acylation on the stability and solubility of lens proteins and determine whether acylation can be used to
improve the compromised resilience of aged human lenses.

## Key facts

- **NIH application ID:** 10189596
- **Project number:** 5R01EY028836-04
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Ram H Nagaraj
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $415,209
- **Award type:** 5
- **Project period:** 2018-09-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10189596

## Citation

> US National Institutes of Health, RePORTER application 10189596, Acylation of Lens Proteins (5R01EY028836-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10189596. Licensed CC0.

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