7P70

The PDZ-domain of SNTB1 complexed with the PDZ-binding motif of HPV35-E6

Summary for 7P70

• Entry DOI: 10.2210/pdb7p70/pdb
• Descriptor: Protein E6, Beta-1-syntrophin,Annexin A2, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: pdz, complex, peptide binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 48620.57

Authors

Gogl, G.,Cousido-Siah, A.,Trave, G. (deposition date: 2021-07-19, release date: 2022-07-27, Last modification date: 2024-02-07)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2 Å)