Functional control of a 0.5 MDa TET aminopeptidase by a flexible loop revealed by MAS NMR

Diego F. Gauto, Pavel Macek, Duccio Malinverni, Hugo Fraga, Matteo Paloni, Iva Sučec, Audrey Hessel, Juan Pablo Bustamante, Alessandro Barducci () and Paul Schanda ()
Additional contact information
Diego F. Gauto: Univ. Grenoble Alpes, CEA, CNRS, Institut de Biologie Structurale (IBS)
Pavel Macek: Univ. Grenoble Alpes, CEA, CNRS, Institut de Biologie Structurale (IBS)
Duccio Malinverni: St Jude Children’s Research Hospital
Hugo Fraga: Univ. Grenoble Alpes, CEA, CNRS, Institut de Biologie Structurale (IBS)
Matteo Paloni: Univ Montpellier, CNRS, INSERM
Iva Sučec: Univ. Grenoble Alpes, CEA, CNRS, Institut de Biologie Structurale (IBS)
Audrey Hessel: Univ. Grenoble Alpes, CEA, CNRS, Institut de Biologie Structurale (IBS)
Juan Pablo Bustamante: IBB (CONICET-UNER)
Alessandro Barducci: Univ Montpellier, CNRS, INSERM
Paul Schanda: Univ. Grenoble Alpes, CEA, CNRS, Institut de Biologie Structurale (IBS)

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract Large oligomeric enzymes control a myriad of cellular processes, from protein synthesis and degradation to metabolism. The 0.5 MDa large TET2 aminopeptidase, a prototypical protease important for cellular homeostasis, degrades peptides within a ca. 60 Å wide tetrahedral chamber with four lateral openings. The mechanisms of substrate trafficking and processing remain debated. Here, we integrate magic-angle spinning (MAS) NMR, mutagenesis, co-evolution analysis and molecular dynamics simulations and reveal that a loop in the catalytic chamber is a key element for enzymatic function. The loop is able to stabilize ligands in the active site and may additionally have a direct role in activating the catalytic water molecule whereby a conserved histidine plays a key role. Our data provide a strong case for the functional importance of highly dynamic - and often overlooked - parts of an enzyme, and the potential of MAS NMR to investigate their dynamics at atomic resolution.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-29423-0 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:13:y:2022:i:1:d:10.1038_s41467-022-29423-0

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

DOI: 10.1038/s41467-022-29423-0

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 ().