9z30

Solution NMR Structure of the PACS1 Furin binding region (FBR)

spinqualitylabelsall models 9z30 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9z30 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR, models Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The c607C>T mutation in the PACS1 gene results in an Arg203Trp substitution in the multifunctional protein PACS-1, and drives a syndrome characterized by intellectual disability, seizures, craniofacial dysmorphisms, and various characteristics of the autism spectrum. On the molecular level, this syndrome, in part, results from enhanced association of PACS-1 with the protein deacetylase HDAC6. PACS-1 uses its Furin binding region (FBR: amino acids 101-273) to directly interact with the catalytic domains of HDAC6. We present the solution structure of a chimeric PACS-1 FBR and use NMR to demonstrate that the PACS-1/HDAC6 interaction is regulated by an intramolecular mechanism involving the central unstructured region of PACS-1 folding back across the FBR and engaging in contacts with an extended, positively charged loop. The R203W substitution, located in this loop, disrupts this regulatory interaction and, in vitro, displays the ability to promote aberrant protein-protein interactions. The R203W substitution drives PACS-1 syndrome by disrupting intramolecular regulation.,Krzysiak TC, Byeon IL, Ponticelli R, Lucas ME, Thompson L, DeHaven C, Thomas G, Gronenborn AM FEBS J. 2026 Mar 20. doi: 10.1111/febs.70492. PMID:41858172 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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