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ID 118953
Author
Miyajima, Rin Tokushima University
Tanegashima, Kosuke Tokyo Metropolitan Institute of Medical Science
Naruse, Naoto Tokushima University
Hara, Takahiko Tokyo Metropolitan Institute of Medical Science|Tokyo Medical and Dental University|Tokyo Metropolitan University
Content Type
Journal Article
Description
CXCL14 is a primordial CXC-type chemokine that transports CpG oligodeoxynucleotides (ODN) into endosomes and lysosomes in dendritic cells, thereby leading to activation of the Toll-like receptor 9 (TLR9)-mediated innate immune system. However, the underlying molecular mechanism by which CXCL14-CpG ODN complex enter cells remains elusive. Herein, we describe the chemical synthesis of CXCL14-derived photoaffinity probes and their application to identification of target receptors for CXCL14 using quantitative proteomics. By utilizing native chemical ligation and maleimide-thiol coupling chemistry, we synthesized site-specifically modified CXCL14-based photoaffinity probes that contain photoreactive 2-aryl-5-carboxytetrazole (ACT) and a hydrazine labile cleavable linker. CXCL14-based probes were found to be capable of binding CpG ODN to immune cells, whose bioactivities were comparable to native CXCL14. Application of CXCL14-derived probes to quantitative proteomic experiments enabled identification of dozens of target receptor candidates for CXCL14 in mouse macrophage-derived RAW264.7 cells, and we discovered that low-density lipoprotein receptor-related protein 1 (LRP1) is a novel receptor for CXCL14 by competitive proteome profiling. We further showed that disruption of LRP1 affected incorporation of CXCL14-CpG ODN complex in the cells. Overall, this report highlights the power of synthetic CXCL14-derived photoaffinity probes combined with chemical proteomics to discover previously unidentified receptors for CXCL14, which could promote understanding of the molecular functions of CXCL14 and the elaborate machinery of innate immune systems.
Journal Title
ACS Chemical Biology
ISSN
15548929
15548937
NCID
AA1212269X
AA12416577
Publisher
ACS Publications
Volume
19
Issue
2
Start Page
551
End Page
562
Published Date
2024-01-30
Remark
論文本文は2025-01-30以降公開予定
Rights
This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Chemical Biology, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acschembio.3c00717.
DOI (Published Version)
URL ( Publisher's Version )
language
eng
TextVersion
その他
departments
Pharmaceutical Sciences