5EKI

Crystal Structure of Truncated CCL21

5EKI の概要

• エントリーDOI: 10.2210/pdb5eki/pdb
• 分子名称: C-C motif chemokine 21, SULFATE ION (3 entities in total)
• 機能のキーワード: cytokine, chemokine, chemotaxis, inflammation, immune system
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 53666.02

構造登録者

Lewandowski, E.M.,Smith, E.W.,Chen, Y. (登録日: 2015-11-03, 公開日: 2016-10-05, 最終更新日: 2024-10-16)

主引用文献

Smith, E.W.,Lewandowski, E.M.,Moussouras, N.A.,Kroeck, K.G.,Volkman, B.F.,Veldkamp, C.T.,Chen, Y.
Crystallographic Structure of Truncated CCL21 and the Putative Sulfotyrosine-Binding Site.
Biochemistry, 55:5746-5753, 2016

PubMed 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.

PubMed: 27617343
DOI: 10.1021/acs.biochem.6b00304

実験手法

X-RAY DIFFRACTION (1.9 Å)