Crowding-Induced Elongated Conformation of Urea-Unfolded Apoazurin: Investigating the Role of Crowder Shape in Silico

Fabio C. Zegarra, Dirar Homouz, Andrei G. Gasic, Lucas Babel, Michael Kovermann, Pernilla Wittung-Stafshede, Margaret S. Cheung

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Here, we show by solution nuclear magnetic resonance measurements that the urea-unfolded protein apoazurin becomes elongated when the synthetic crowding agent dextran 20 is present, in contrast to the prediction from the macromolecular crowding effect based on the argument of volume exclusion. To explore the complex interactions beyond volume exclusion, we employed coarse-grained molecular dynamics simulations to explore the conformational ensemble of apoazurin in a box of monodisperse crowders under strong chemically denaturing conditions. The elongated conformation of unfolded apoazurin appears to result from the interplay of the effective attraction between the protein and crowders and the shape of the crowders. With a volume-conserving crowder model, we show that the crowder shape provides an anisotropic direction of the depletion force, in which a bundle of surrounding rodlike crowders stabilize an elongated conformation of unfolded apoazurin in the presence of effective attraction between the protein and crowders.

Original languageBritish English
Pages (from-to)3607-3617
Number of pages11
JournalJournal of Physical Chemistry B
Volume123
Issue number17
DOIs
StatePublished - 2 May 2019

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