Charge Interactions Can Dominate Coupled Folding and Binding on the Ribosome

Biophysical Journal
Jacopo MarinoBenjamin Schuler

Abstract

Interactions between emerging nascent polypeptide chains and the ribosome can modulate cotranslational protein folding. However, it has remained unclear how such interactions can affect the binding of nascent chains to their cellular targets. We thus investigated on the ribosome the interaction between two intrinsically disordered proteins of opposite charge, ACTR and NCBD, which form a high-affinity complex in a coupled folding-and-binding reaction. Using fluorescence correlation spectroscopy and arrest-peptide-mediated force measurements in vitro and in vivo, we find that the ACTR-NCBD complex can form cotranslationally but only with ACTR as the nascent chain and NCBD free in solution, not vice versa. We show that this surprising asymmetry in behavior is caused by pronounced charge interactions: attraction of the positively charged nascent chain of NCBD to the negatively charged ribosomal surface competes with complex formation and prevents ACTR binding. In contrast, the negatively charged nascent ACTR is repelled by the ribosomal surface and thus remains available for productively binding its partner. Electrostatic interactions may thus be more important for cotranslational folding and binding than previously thought.

Citations

Jul 28, 2019·Current Protein & Peptide Science·Seong Il Choi
Jun 23, 2020·Annual Review of Biochemistry·Anaïs M E CassaignauJohn Christodoulou
Jan 16, 2020·Biomolecules·Marija LiutkuteMarina V Rodnina
Dec 1, 2020·Current Opinion in Structural Biology·Gopika GopanMeredith Rickard
Apr 30, 2020·The Journal of Physical Chemistry. B·Yani ZhaoJoseph F Rudzinski
May 29, 2019·Biochemistry·Sarah E LeiningerEdward P O'Brien
Oct 16, 2021·Nature Chemistry·Anaïs M E CassaignauJohn Christodoulou

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