5H9W

Crystal structure of Regnase PIN domain, form II

Summary for 5H9W

• Entry DOI: 10.2210/pdb5h9w/pdb
• Related: 5H9V
• Descriptor: Ribonuclease ZC3H12A, SODIUM ION (3 entities in total)
• Functional Keywords: rnase, hydrolase
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 2
• Total formula weight: 49106.56

Authors

Yokogawa, M.,Tsushima, T.,Adachi, W.,Noda, N.N.,Inagaki, F. (deposition date: 2015-12-29, release date: 2016-03-16, Last modification date: 2023-11-08)

Primary citation

Yokogawa, M.,Tsushima, T.,Noda, N.N.,Kumeta, H.,Enokizono, Y.,Yamashita, K.,Standley, D.M.,Takeuchi, O.,Akira, S.,Inagaki, F.
Structural basis for the regulation of enzymatic activity of Regnase-1 by domain-domain interactions
Sci Rep, 6:22324-22324, 2016

PubMed Abstract: Regnase-1 is an RNase that directly cleaves mRNAs of inflammatory genes such as IL-6 and IL-12p40, and negatively regulates cellular inflammatory responses. Here, we report the structures of four domains of Regnase-1 from Mus musculus-the N-terminal domain (NTD), PilT N-terminus like (PIN) domain, zinc finger (ZF) domain and C-terminal domain (CTD). The PIN domain harbors the RNase catalytic center; however, it is insufficient for enzymatic activity. We found that the NTD associates with the PIN domain and significantly enhances its RNase activity. The PIN domain forms a head-to-tail oligomer and the dimer interface overlaps with the NTD binding site. Interestingly, mutations blocking PIN oligomerization had no RNase activity, indicating that both oligomerization and NTD binding are crucial for RNase activity in vitro. These results suggest that Regnase-1 RNase activity is tightly controlled by both intramolecular (NTD-PIN) and intermolecular (PIN-PIN) interactions.

PubMed: 26927947
DOI: 10.1038/srep22324

Experimental method

X-RAY DIFFRACTION (2.6 Å)