PDBsum entry 4g8l

Hydrolase

PDB id: 4g8l

Contents

Protein chain

307 a.a.

Ligands

25A ×4

PDB id:

4g8l

Name:

Hydrolase

Title:

Active state of intact sensor domain of human rnase l with 2-5a bound

Structure:

2-5a-dependent ribonuclease. Chain: a, b, c, d. Fragment: 2-5a-sensor domain (ank domain). Synonym: 2-5a-dependent rnase, ribonuclease 4, ribonuclease l, rnase l. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: rnasel, rns4. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.80Å R-factor: 0.230 R-free: 0.261

Authors:

Y.Han,G.Whitney,J.Donovan,A.Korennykh

Key ref:

Y.Han et al. (2012). Innate immune messenger 2-5A tethers human RNase L into active high-order complexes. Cell Rep, 2, 902-913. PubMed id: 23084743 DOI: 10.1016/j.celrep.2012.09.004

Date:

23-Jul-12 Release date: 31-Oct-12

Protein chains

Q05823  (RN5A_HUMAN) -  2-5A-dependent ribonuclease from Homo sapiens

Seq: 741 a.a.

Struc: 307 a.a.

Enzyme reactions

• Enzyme class: E.C.3.1.26.- - ?????

DOI no: 10.1016/j.celrep.2012.09.004

Cell Rep 2:902-913 (2012)

PubMed id: 23084743

Innate immune messenger 2-5A tethers human RNase L into active high-order complexes.

Y.Han, G.Whitney, J.Donovan, A.Korennykh.

ABSTRACT

2',5'-linked oligoadenylates (2-5As) serve as conserved messengers of pathogen presence in the mammalian innate immune system. 2-5As induce self-association and activation of RNase L, which cleaves cytosolic RNA and promotes the production of interferons (IFNs) and cytokines driven by the transcription factors IRF-3 and NF-κB. We report that human RNase L is activated by forming high-order complexes, reminiscent of the mode of activation of the phylogenetically related transmembrane kinase/RNase Ire1 in the unfolded protein response. We describe crystal structures determined at 2.4 Å and 2.8 Å resolution, which show that two molecules of 2-5A at a time tether RNase L monomers via the ankyrin-repeat (ANK) domain. Each ANK domain harbors two distinct sites for 2-5A recognition that reside 50 Å apart. These data reveal a function for the ANK domain as a 2-5A-sensing homo-oligomerization device and describe a nonlinear, ultrasensitive regulation in the 2-5A/RNase L system poised for amplification of the IFN response.