creators_name: Bajaj, Manish
creators_name: Muddassir, Mohd
creators_name: Choi, Bumjoon 
creators_name: Singh, Priyanka 
creators_name: Park, Jong Bum 
creators_name: Singh, Surjeet
creators_name: Yadav, Manisha
creators_name: Kumar, Rajesh
creators_name: Eom, Kilho
creators_name: Sharma, Deepak 
creators_id:  
type: article
datestamp: 2024-07-16 02:08:58
lastmod: 2024-07-16 02:08:58
metadata_visibility: show
title: Single-molecule analysis of osmolyte-mediated nanomechanical unfolding behavior of a protein domain

ispublished: pub
subjects: QR
keywords:  Mechanical stability; Protein unfolding; Single-molecule force spectroscopy.
note: The copyright of this article belongs to Elsevier Science
abstract: The small organic molecules, known as osmolytes being ubiquitously present in different cell types, affect protein folding, stability and aggregation. However, it is unknown how the osmolytes affect the nanomechanical unfolding behavior of protein domain. Here, we show the osmolyte-dependent mechanical unfolding properties of protein titin immunoglobulin-27 (I27) domain using an atomic force microscopy (AFM)-based single-molecule force spectroscopy. We found that amines and methylamines improved the mechanical stability of I27 domain, whereas polyols had no effect. Interestingly, glycine betaine (GB) or trimethylamine-N-oxide (TMAO) increased the average unfolding force of the protein domain. The kinetic parameters analyzed at single-molecule level reveal that stabilizing effect of osmolytes is due to a decrease in the unfolding rate constant of I27, which was confirmed by molecular dynamics simulations. Our study reveals different effects that diverse osmolytes have on the mechanical properties of the protein, and suggests the potential use of osmolytes in modulating the mechanical stability of proteins required for various nano-biotechnological applications.


date: 2023-12-31
date_type: published
publication: International journal of biological macromolecules
volume: 253
publisher: Elsevier Science
id_number: 10.1016/j.ijbiomac.2023.126849
refereed: TRUE
issn: 1879-0003
official_url: https://www.sciencedirect.com/science/article/pii/S0141813023037467?via%3Dihub
citation:   Bajaj, Manish and Muddassir, Mohd and Choi, Bumjoon  and Singh, Priyanka  and Park, Jong Bum  and Singh, Surjeet and Yadav, Manisha and Kumar, Rajesh and Eom, Kilho and Sharma, Deepak   (2023) Single-molecule analysis of osmolyte-mediated nanomechanical unfolding behavior of a protein domain.  International journal of biological macromolecules, 253.   ISSN 1879-0003