7p74 | pdb_00007p74
The PDZ domain of SYNJ2BP complexed with the phosphorylated PDZ-binding motif of RSK1
Structural highlights
FunctionANXA2_HUMAN Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids. It binds two calcium ions with high affinity. May be involved in heat-stress response.SYJ2B_HUMAN Publication Abstract from PubMedHuman 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. Quantitative fragmentomics allow affinity mapping of interactomes.,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 Nat Commun. 2022 Sep 17;13(1):5472. doi: 10.1038/s41467-022-33018-0. PMID:36115835[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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