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

The neutrophil gelatinase-associated lipocalin (NGAL, also known as LCN2) and its cellular receptor (LCN2-R, SLC22A17) are involved in many physiological and pathological processes such as cell differentiation, apoptosis, and inflammation. These pleiotropic functions mainly rely on NGAL's sider...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2016-02, Vol.291 (6), p.2917-2930
Main Authors: Cabedo Martinez, Ana-Isabel, Weinhäupl, Katharina, Lee, Wing-Kee, Wolff, Natascha A., Storch, Barbara, Żerko, Szymon, Konrat, Robert, Koźmiński, Wiktor, Breuker, Kathrin, Thévenod, Frank, Coudevylle, Nicolas
Format: Article
Language:English
Subjects:
Acute-Phase Proteins - chemistry
Acute-Phase Proteins - genetics
Acute-Phase Proteins - metabolism
Animals
cell surface protein
CHO Cells
Cricetinae
Cricetulus
fuzzy complex
Humans
intrinsically disordered protein
Lipocalin-2
Lipocalins - chemistry
Lipocalins - genetics
Lipocalins - metabolism
membrane protein
Mice
neutrophil gelatinase-associated lipocalin receptor
Nuclear Magnetic Resonance, Biomolecular
Organic Cation Transport Proteins - chemistry
Organic Cation Transport Proteins - genetics
Organic Cation Transport Proteins - metabolism
Protein Binding
protein complex
Protein Structure and Folding
Protein Structure, Tertiary
protein-protein interaction
Proto-Oncogene Proteins - chemistry
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The neutrophil gelatinase-associated lipocalin (NGAL, also known as LCN2) and its cellular receptor (LCN2-R, SLC22A17) are involved in many physiological and pathological processes such as cell differentiation, apoptosis, and inflammation. These pleiotropic functions mainly rely on NGAL's 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 (≈10 μm) between human LCN2-R-NTD and apoNGAL suggests that the N terminus on its own cannot account for the internalization of NGAL by LCN2-R. However, human LCN2-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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M115.685644