Lysine acetylation regulates the interaction between proteins and membranes

Alan K. Okada, Kazuki Teranishi, Mark R. Ambroso, Jose Mario Isas, Elena Vazquez-Sarandeses, Joo-Yeun Lee, Arthur Alves Melo, Priyatama Pandey, Daniel Merken, Leona Berndt, Michael Lammers, Oliver Daumke, Karen Chang, Ian S. Haworth and Ralf Langen ()
Additional contact information
Alan K. Okada: Regions Hospital Department of Emergency Medicine
Kazuki Teranishi: University of Southern California
Mark R. Ambroso: University of Southern California
Jose Mario Isas: University of Southern California
Elena Vazquez-Sarandeses: Max-Delbrück-Center for Molecular Medicine, Crystallography
Joo-Yeun Lee: University of Southern California
Arthur Alves Melo: Max-Delbrück-Center for Molecular Medicine, Crystallography
Priyatama Pandey: University of Southern California
Daniel Merken: University of Southern California
Leona Berndt: University of Greifswald
Michael Lammers: University of Greifswald
Oliver Daumke: Max-Delbrück-Center for Molecular Medicine, Crystallography
Karen Chang: University of Southern California
Ian S. Haworth: University of Southern California
Ralf Langen: University of Southern California

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract Lysine acetylation regulates the function of soluble proteins in vivo, yet it remains largely unexplored whether lysine acetylation regulates membrane protein function. Here, we use bioinformatics, biophysical analysis of recombinant proteins, live-cell fluorescent imaging and genetic manipulation of Drosophila to explore lysine acetylation in peripheral membrane proteins. Analysis of 50 peripheral membrane proteins harboring BAR, PX, C2, or EHD membrane-binding domains reveals that lysine acetylation predominates in membrane-interaction regions. Acetylation and acetylation-mimicking mutations in three test proteins, amphiphysin, EHD2, and synaptotagmin1, strongly reduce membrane binding affinity, attenuate membrane remodeling in vitro and alter subcellular localization. This effect is likely due to the loss of positive charge, which weakens interactions with negatively charged membranes. In Drosophila, acetylation-mimicking mutations of amphiphysin cause severe disruption of T-tubule organization and yield a flightless phenotype. Our data provide mechanistic insights into how lysine acetylation regulates membrane protein function, potentially impacting a plethora of membrane-related processes.

Date: 2021
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (6)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-26657-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26657-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-26657-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().