7QCR

MLLT4/Afadin PDZ domain in complex with the C-terminal peptide from protein E of SARS-CoV-2

7QCR の概要

• エントリーDOI: 10.2210/pdb7qcr/pdb
• 分子名称: Afadin, Envelope small membrane protein, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: mllt4-afadin pdz domain in complex with the c-terminal peptide from protein e of sars-cov-2, cell adhesion
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 22878.23

構造登録者

Zhu, Y.,Alvarez, F.,Haouz, A.,Mechaly, A.,Caillet-Saguy, C. (登録日: 2021-11-25, 公開日: 2022-04-20, 最終更新日: 2024-01-31)

主引用文献

Zhu, Y.,Alvarez, F.,Wolff, N.,Mechaly, A.,Brule, S.,Neitthoffer, B.,Etienne-Manneville, S.,Haouz, A.,Boeda, B.,Caillet-Saguy, C.
Interactions of Severe Acute Respiratory Syndrome Coronavirus 2 Protein E With Cell Junctions and Polarity PSD-95/Dlg/ZO-1-Containing Proteins.
Front Microbiol, 13:829094-829094, 2022

PubMed Abstract: The C-terminus of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protein E contains a PBM (PDZ-binding motif) targeting PDZ (PSD-95/Dlg/ZO-1) domains, which is identical to the PBM of SARS-CoV. The latter is involved in the pathogenicity of the virus. Recently, we identified 10 human PDZ-containing proteins showing significant interactions with SARS-CoV-2 protein E PBM. We selected several of them involved in cellular junctions and cell polarity (TJP1, PARD3, MLLT4, and LNX2) and MPP5/PALS1 previously shown to interact with SARS-CoV E PBM. Targeting cellular junctions and polarity components is a common strategy by viruses to hijack cell machinery to their advantage. In this study, we showed that these host PDZ domains TJP1, PARD3, MLLT4, LNX2, and MPP5/PALS1 interact in a PBM-dependent manner and colocalize with the full-length E protein , sequestrating the PDZ domains to the Golgi compartment. We solved three crystal structures of complexes between human LNX2, MLLT4, and MPP5 PDZs and SARS-CoV-2 E PBM highlighting its binding preferences for several cellular targets. Finally, we showed different affinities for the PDZ domains with the original SARS-CoV-2 C-terminal sequence containing the PBM and the one of the beta variant that contains a mutation close to the PBM. The acquired mutations in the E protein localized near the PBM might have important effects both on the structure and the ion-channel activity of the E protein and on the host machinery targeted by the variants during the infection.

PubMed: 35283834
DOI: 10.3389/fmicb.2022.829094

実験手法

X-RAY DIFFRACTION (2.28 Å)