Size-dependent studies of macromolecular crowding on the thermodynamic stability, structure and functional activity of proteins: in vitro and in silico approaches

• Published in: Biochimica et biophysica acta. General subjects Vol. 1861; no. 2; pp. 178 - 197
• Main Authors: Shahid, Sumra, Hassan, Md. Imtaiyaz, Islam, Asimul, Ahmad, Faizan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2017
• Subjects: Animals; Computer Simulation; Crowder size; Excluded volume effect; Functional activity; Humans; in vitro studies; M D simulation; Macromolecular crowding; Macromolecular Substances - chemistry; Protein Conformation; Protein Folding; proteins; Proteins - chemistry; solvents; Structure-Activity Relationship; Thermodynamic stability; Thermodynamics; Km; Functional activity; ANS; HRP; mi-CK; CRABP I; M D simulation; GdmCl; MDH; BSA; LDH; Trp; PDI; bOBP; SPT; HSA; Tm; FRET; Macromolecular crowding; AMPPNP; GN; Thermodynamic stability; Crowder size; GAPD; ΔΔGND; r; PEG; FKBP; ΔHm; Excluded volume effect; kcat; Kd
• ISSN: 0304-4165; 1872-8006
• DOI: 10.1016/j.bbagen.2016.11.014

The environment inside cells in which proteins fold and function are quite different from that of the dilute buffer solutions often used during in vitro experiments. The presence of large amounts of macromolecules of varying shapes, sizes and compositions makes the intracellular milieu extremely crowded. The overall concentration of macromolecules ranges from 50 to 400gl−1, and they occupy 10–40% of the total cellular volume. These differences in solvent conditions and the level of crowdedness resulting in excluded volume effects can have significant consequences on proteins' biophysical properties. A question that arises is: how important is it to examine the roles of shape, size and composition of macromolecular crowders in altering the biological properties of proteins? This review article aims at focusing, gathering and summarizing all of the research investigations done by means of in vitro and in silico approaches taking into account the size-dependent influence of the crowders on proteins' properties. Altogether, the internal architecture of macromolecular crowding environment including size, shape and concentration of crowders, appears to be playing an extremely important role in causing changes in the biological processes. Most often the small sized crowders have been found more effective crowding agents. However, thermodynamic stability, structure and functional activity of proteins have been governed by volume exclusion as well as soft (chemical) interactions. The article provides an understanding of importance of internal architecture of the cellular environment in altering the biophysical properties of proteins. [Display omitted] •First review on size–dependent studies of macromolecular crowding•Internal architecture of macromolecular crowding plays a significant role.•It affects stability, structure and functional activity of proteins.•Volume exclusion due to interdependence of concentration and size of the crowder.•Small sized crowders have been found to be more effective.