Biochemical and Structural Characterization of the Interaction between the Siderocalin NGAL/LCN2 (Neutrophil Gelatinase-associated Lipocalin/Lipocalin 2) and the N-terminal Domain of Its Endocytic Receptor SLC22A17
- Author(s)
- Ana-Isabel Cabedo Martinez, Katharina Weinhaupl, Wing-Kee Lee, Natascha A Wolff, Barbara Storch, Szymon Żerko, Robert Konrat, Wiktor Koźmiński, Kathrin Breuker, Frank Thévenod, Nicolas Coudevylle
- Abstract
The neutrophil gelatinase associated lipocalin (NGAL, aslo known as LCN2) and its cellular receptor (LCN2-R) are involved in many physiological and pathological processes such as cell differentiation, apoptosis and inflammation. These pleiotropic functions mainly rely on NGALs siderophore mediated iron transport properties. However the molecular determinants underlying the interaction between NGAL and its cellular receptor remain largely unknown. Here, using solution-state biomolecular NMR in conjunction with other biophysical methods, we show that the N-terminal domain of LCN2-R is a soluble extracellular domain that is intrinsically disordered and interacts with NGAL preferentially in its apo-state to form a fuzzy complex. The relatively weak affinity (≈ 10μM) between hLCN2-R-NTD and apoNGAL suggests that the N-terminus on its own cannot account for the internalization of NGAL by LCN2-R. However, hLCN2-R-NTD could be involved in the fine-tuning of the interaction between NGAL and its cellular receptor, or in a biochemical mechanism allowing the receptor to discriminate between apo- and holo-NGAL.
- Organisation(s)
- Department of Structural and Computational Biology
- External organisation(s)
- Universität Witten/Herdecke, Leopold-Franzens-Universität Innsbruck, University of Warsaw, Max F. Perutz Laboratories GmbH (MFPL)
- Journal
- Journal of Biological Chemistry
- Volume
- 291
- Pages
- 2917-2930
- No. of pages
- 14
- ISSN
- 0021-9258
- DOI
- https://doi.org/10.1074/jbc.M115.685644
- Publication date
- 02-2016
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 106041 Structural biology
- Keywords
- ASJC Scopus subject areas
- Molecular Biology, Biochemistry, Cell Biology
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/fe7d0eaa-5471-4a0b-afc3-190ebb60daca