9IPL

A tetrapyrrole binding domain variant of CoaR in closed conformation at 2.28 angstrom resolution

Summary for 9IPL

• Entry DOI: 10.2210/pdb9ipl/pdb
• Descriptor: Mercuric resistance operon regulatory protein precorrin isomerase, SULFATE ION (3 entities in total)
• Functional Keywords: tetrapyrrole binding, coar, cobalt binding, metal binding protein
• Biological source: Synechocystis sp. (strain PCC 6803 / Kazusa)
• Total number of polymer chains: 2
• Total formula weight: 47448.01

Authors

Liu, X.C. (deposition date: 2024-07-10, release date: 2025-07-16, Last modification date: 2026-07-15)

Primary citation

Liu, X.,Guo, P.,Yu, Q.,Gao, S.Q.,Yuan, H.,Tan, X.,Lin, Y.W.
Site-specific incorporation of 19 F-nulcei at protein C-terminus to probe allosteric conformational transitions of metalloproteins.
Commun Biol, 7:1613-1613, 2024

PubMed Abstract: Allosteric conformational change is an important paradigm in the regulation of protein function, which is typically triggered by the binding of small cofactors, metal ions or protein partners. Here, we found those conformational transitions can be effectively monitored by F NMR, facilitated by a site-specific F incorporation strategy at the protein C-terminus using asparaginyl endopeptidase (AEP). Three case studies show that C-terminal F-nuclei can reveal protein dynamics not only adjacent but also distal to C-terminus, including those occurring in a hemoprotein neuroglobin (Ngb), calmodulin (CaM), and a cobalt metalloregulator (CoaR) responding to both cobalt and tetrapyrrole. In Ngb, the heme orientation disorder is affected by missense mutations that perturb backbone rigidity or surface charges close to the heme axial ligands. In CaM, the C-terminal F-nuclei is an ideal probe for detecting the binding states of Ca, peptides and inhibitors. Furthermore, multiple F-moieties were incorporated into the two domains of CoaR, revealing the intrinsically disordered C-terminal metal binding tail might be an allosteric conformational switch to maintain cobalt homeostasis and balance corrinoid biosynthesis. This study demonstrates that the AEP-based F-modification strategy can be applied to various targets to study allosteric regulation, especially for those biological processes modulated by the protein C-terminus.

PubMed: 39627324
DOI: 10.1038/s42003-024-07331-x

Experimental method

X-RAY DIFFRACTION (2.28 Å)