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Publication Abstract from PubMed

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 solved the X-ray crystallographic structure of a truncated CCL21 (residues 1-79) lacking the extended C-terminus, and identified, via 2D NMR, a putative sulfotyrosine-binding site that may recognize such post-translationally modified tyrosine residues on the receptor. Compared to the previously solved 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 the full length CCL21 can interact with this important region for receptor binding. These observations suggest a potential origin for the auto-inhibition 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.

Crystallographic structure of truncated CCL21 and putative sulfotyrosine-binding site.,Smith EW, Lewandowski EM, Moussouras NA, Kroeck KG, Volkman BF, Veldkamp CT, Chen Y Biochemistry. 2016 Sep 12. PMID:27617343^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.