5EKI

Crystal Structure of Truncated CCL21

Summary for 5EKI

• Entry DOI: 10.2210/pdb5eki/pdb
• Descriptor: C-C motif chemokine 21, SULFATE ION (3 entities in total)
• Functional Keywords: cytokine, chemokine, chemotaxis, inflammation, immune system
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 6
• Total formula weight: 53666.02

Authors

Lewandowski, E.M.,Smith, E.W.,Chen, Y. (deposition date: 2015-11-03, release date: 2016-10-05, Last modification date: 2024-10-16)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.9 Å)