4ZLT

Crystal structure of viral chemokine binding protein R17 in complex with CCL3

Summary for 4ZLT

• Entry DOI: 10.2210/pdb4zlt/pdb
• Related: 2X6G 4ZKQ
• Descriptor: Putative uncharacterized protein, C-C motif chemokine 3, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: rhvp chemokine binding protein in complex with chemokine ccl3, chemokine binding protein-chemokine complex, chemokine binding protein/chemokine
• Biological source: Cricetid herpesvirus 2; More
• Total number of polymer chains: 4
• Total formula weight: 111626.21

Authors

Lubman, O.Y.,Fremont, D.H. (deposition date: 2015-05-01, release date: 2015-11-18, Last modification date: 2024-11-13)

Primary citation

Lubman, O.Y.,Fremont, D.H.
Parallel Evolution of Chemokine Binding by Structurally Related Herpesvirus Decoy Receptors.
Structure, 24:57-69, 2016

PubMed Abstract: A wide variety of pathogens targets chemokine signaling networks in order to disrupt host immune surveillance and defense. Here, we report a structural and mutational analysis of rodent herpesvirus Peru encoded R17, a potent chemokine inhibitor that sequesters CC and C chemokines with high affinity. R17 consists of a pair of β-sandwich domains linked together by a bridging sheet, which form an acidic binding cleft for the chemokine CCL3 on the opposite face of a basic surface cluster that binds glycosaminoglycans. R17 promiscuously engages chemokines primarily through the same N-loop determinants used for host receptor recognition while residues located in the chemokine 40s loop drive kinetically stable complex formation. The core fold adopted by R17 is unexpectedly similar to that of the M3 chemokine decoy receptor encoded by MHV-68, although, strikingly, neither the location of ligand engagement nor the stoichiometry of binding is conserved, suggesting that their functions evolved independently.

PubMed: 26671708
DOI: 10.1016/j.str.2015.10.018

Experimental method

X-RAY DIFFRACTION (3 Å)