5WB1

Ligand-free US28 with stabilizing intracellular nanobody

5WB1 の概要

• エントリーDOI: 10.2210/pdb5wb1/pdb
• 分子名称: Envelope protein US28, nanobody 7 fusion protein (1 entity in total)
• 機能のキーワード: chemokine receptor, membrane protein
• 由来する生物種: Human cytomegalovirus (HHV-5); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 51827.99

構造登録者

Jude, K.M.,Burg, J.S.,Garcia, K.C. (登録日: 2017-06-27, 公開日: 2018-06-13, 最終更新日: 2024-10-23)

主引用文献

Miles, T.F.,Spiess, K.,Jude, K.M.,Tsutsumi, N.,Burg, J.S.,Ingram, J.R.,Waghray, D.,Hjorto, G.M.,Larsen, O.,Ploegh, H.L.,Rosenkilde, M.M.,Garcia, K.C.
Viral GPCR US28 can signal in response to chemokine agonists of nearly unlimited structural degeneracy.
Elife, 7:-, 2018

PubMed Abstract: Human cytomegalovirus has hijacked and evolved a human G-protein-coupled receptor into US28, which functions as a promiscuous chemokine 'sink' to facilitate evasion of host immune responses. To probe the molecular basis of US28's unique ligand cross-reactivity, we deep-sequenced CX3CL1 chemokine libraries selected on 'molecular casts' of the US28 active-state and find that US28 can engage thousands of distinct chemokine sequences, many of which elicit diverse signaling outcomes. The structure of a G-protein-biased CX3CL1-variant in complex with US28 revealed an entirely unique chemokine amino terminal peptide conformation and remodeled constellation of receptor-ligand interactions. Receptor signaling, however, is remarkably robust to mutational disruption of these interactions. Thus, US28 accommodates and functionally discriminates amongst highly degenerate chemokine sequences by sensing the steric bulk of the ligands, which distort both receptor extracellular loops and the walls of the ligand binding pocket to varying degrees, rather than requiring sequence-specific bonding chemistries for recognition and signaling.

PubMed: 29882741
DOI: 10.7554/eLife.35850

実験手法

X-RAY DIFFRACTION (3.508 Å)