7P71

The PDZ domain of MAGI1_2 complexed with the PDZ-binding motif of HPV35-E6

7P71 の概要

• エントリーDOI: 10.2210/pdb7p71/pdb
• 分子名称: Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1,Annexin A2, Protein E6, CALCIUM ION, ... (6 entities in total)
• 機能のキーワード: pdz, complex, peptide binding protein
• 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: 100246.14

構造登録者

Gogl, G.,Cousido-Siah, A.,Trave, G. (登録日: 2021-07-19, 公開日: 2022-07-27, 最終更新日: 2024-02-07)

主引用文献

Gogl, G.,Zambo, B.,Kostmann, C.,Cousido-Siah, A.,Morlet, B.,Durbesson, F.,Negroni, L.,Eberling, P.,Jane, P.,Nomine, Y.,Zeke, A.,Ostergaard, S.,Monsellier, E.,Vincentelli, R.,Trave, G.
Quantitative fragmentomics allow affinity mapping of interactomes.
Nat Commun, 13:5472-5472, 2022

PubMed Abstract: Human protein networks have been widely explored but most binding affinities remain unknown, hindering quantitative interactome-function studies. Yet interactomes rely on minimal interacting fragments displaying quantifiable affinities. Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer. We calculate interactomic distances, identify hot spots for viral interference, generate binding profiles and specificity logos, and explain selected cases by crystallographic studies. Mass spectrometry experiments on cell extracts and literature surveys show that quantitative fragmentomics effectively complements protein interactomics by providing affinities and completeness of coverage, putting a full human interactome affinity survey within reach. Finally, we show that interactome hijacking by the viral PBM of human papillomavirus E6 oncoprotein substantially impacts the host cell proteome beyond immediate E6 binders, illustrating the complex system-wide relationship between interactome and function.

PubMed: 36115835
DOI: 10.1038/s41467-022-33018-0

実験手法

X-RAY DIFFRACTION (2.6 Å)