Crystallographic Structure of Truncated CCL21 and the Putative Sulfotyrosine-Binding Site
Document Type
Article
Publication Date
2016
Digital Object Identifier (DOI)
https://doi.org/10.1021/acs.biochem.6b00304
Abstract
CCL21 chemokine binds the G protein-coupled receptor CCR7, aiding not only in immune response but also in cancer metastasis. Compared with other chemokines, CCL21 has a unique extended unstructured C-terminus that is truncated in some naturally occurring variants. We have determined the X-ray crystallographic structure of a truncated CCL21 (residues 1–79) lacking the extended C-terminus and identified, via two-dimensional nuclear magnetic resonance (NMR), a putative sulfotyrosine-binding site that may recognize such post-translationally modified tyrosine residues on the receptor. Compared to the previously determined NMR structure of full-length CCL21, the crystal structure presents new druggable binding hot spots resulting from an alternative N-loop conformation. In addition, whereas the previous NMR structure did not provide any structural information after residue 70, the C-terminus of the truncated CCL21, ordered up to Ala77 in our crystal structure, is placed near the N-loop and sulfotyrosine-binding site, indicating that the extended C-terminus of full-length CCL21 can interact with this important region for receptor binding. These observations suggest a potential origin for the autoinhibition of CCL21 activity that was recently described. The new crystal structure and binding hot spot analysis have important implications for the function of the CCL21 C-terminus and drug discovery.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
Biochemistry, v. 55, issue 40, p. 5746-5753
Scholar Commons Citation
Smith, Emmanuel W.; Lewandowski, Eric M.; Moussouras, Natasha A.; Kroeck, Kyle G.; Volkman, Brian F.; Veldkamp, Christopher T.; and Chen, Yu, "Crystallographic Structure of Truncated CCL21 and the Putative Sulfotyrosine-Binding Site" (2016). Molecular Medicine Faculty Publications. 81.
https://digitalcommons.usf.edu/mme_facpub/81
