The macro domain is an ADP-ribose (ADPR) binding module, which is considered to act as a sensor to recognize nicotinamide adenine dinucleotide (NAD) metabolites, including poly ADPR (PAR) and other small molecules. The recognition of macro domains with various ligands is important for a variety of biological functions involved in NAD metabolism, including DNA repair, chromatin remodeling, maintenance of genomic stability, and response to viral infection. Nevertheless, how the macro domain binds to moieties with such structural obstacles using a simple cleft remains a puzzle. We systematically investigated the Middle East respiratory syndrome-coronavirus (MERS-CoV) macro domain for its ligand selectivity and binding properties by structural and biophysical approaches. Of interest, NAD, which is considered not to interact with macro domains, was co-crystallized with the MERS-CoV macro domain. Further studies at physiological temperature revealed that NAD has similar binding ability with ADPR because of the accommodation of the thermal-tunable binding pocket. This study provides the biochemical and structural bases of the detailed ligand-binding mode of the MERS-CoV macro domain. In addition, our observation of enhanced binding affinity of the MERS-CoV macro domain to NAD at physiological temperature highlights the need for further study to reveal the biological functions. Meng-Hsuan Lin et al. investigate MERS-CoV macro domain binding selectivity with NAD and NAD metabolites under various conditions. At physiological temperature, NAD is observed to have enhanced binding affinity to the MERS-CoV macro domain, shedding light on a new possible role of the MERS-CoV macro domain in viral replication.
【저자키워드】 Viral proteins, X-ray crystallography, NMR spectroscopy, 【초록키워드】 Biological functions, viral infection, MERS-CoV, metabolism, binding affinity, Replication, biological function, stability, Small molecules, metabolites, genomic, metabolite, binding, Ligand, DNA repair, Middle East, observation, nicotinamide adenine dinucleotide, biochemical, domains, approaches, domain, physiological temperature, base, binding pocket, chromatin, binding ability, ADP-ribose, highlight, bind, involved, addition, investigated, provide, in viral, recognize, variety, conditions, co-crystallized, 【제목키워드】 MERS-CoV, metabolite, binding, domain,