PDBsum entry 4zya

Ligase

PDB id: 4zya

Contents

Protein chains

69 a.a.

76 a.a.

Ligands

GOL

Metals

_ZN ×2

_CL

Waters ×135

PDB id:

4zya

Name:

Ligase

Title:

The n-terminal extension domain of human asparaginyl-tRNA synthetase

Structure:

Asparagine--tRNA ligase, cytoplasmic. Chain: a, b. Fragment: unp residues 4-77. Synonym: asparaginyl-tRNA synthetase,asnrs. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: nars. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.65Å R-factor: 0.211 R-free: 0.254

Authors:

J.S.Park,M.C.Park,P.Goughnour,H.S.Kim,S.J.Kim,H.J.Kim,S.H.Kim,B.W.Han

Key ref:

J.S.Park et al. (2018). Unique N-terminal extension domain of human asparaginyl-tRNA synthetase elicits CCR3-mediated chemokine activity. Int J Biol Macromol, 120, 835-845. PubMed id: 30171954 DOI: 10.1016/j.ijbiomac.2018.08.171

Date:

21-May-15 Release date: 25-May-16

Protein chain

O43776  (SYNC_HUMAN) -  Asparagine--tRNA ligase, cytoplasmic from Homo sapiens

Seq: 548 a.a.

Struc: 69 a.a.*

Protein chain

O43776  (SYNC_HUMAN) -  Asparagine--tRNA ligase, cytoplasmic from Homo sapiens

Seq: 548 a.a.

Struc: 76 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B: E.C.6.1.1.22 - asparagine--tRNA ligase.
• Reaction: tRNA(Asn) + L-asparagine + ATP = L-asparaginyl-tRNA(Asn) + AMP + diphosphate + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.ijbiomac.2018.08.171

Int J Biol Macromol 120:835-845 (2018)

PubMed id: 30171954

Unique N-terminal extension domain of human asparaginyl-tRNA synthetase elicits CCR3-mediated chemokine activity.

J.S.Park, M.C.Park, K.Y.Lee, P.C.Goughnour, S.J.Jeong, H.S.Kim, H.J.Kim, B.J.Lee, S.Kim, B.W.Han.

ABSTRACT

Asparaginyl-tRNA synthetase (NRS) is not only essential in protein translation but also associated with autoimmune diseases. Particularly, patients with antibodies that recognize NRS often develop interstitial lung disease (ILD). However, the underlying mechanism of how NRS is recognized by immune cells and provokes inflammatory responses is not well-understood. Here, we found that the crystal structure of the unique N-terminal extension domain of human NRS (named as UNE-N, where -N denotes NRS) resembles that of the chemotactic N-terminal domain of NRS from a filarial nematode, Brugia malayi, which recruits and activates specific immune cells by interacting with CXC chemokine receptor 1 and 2. UNE-N induced migration of CC chemokine receptor 3 (CCR3)-expressing cells. The chemokine activity of UNE-N was significantly reduced by suppressing CCR3 expression with CCR3-targeting siRNA, and the loop3 region of UNE-N was shown to interact mainly with the extracellular domains of CCR3 in nuclear magnetic resonance perturbation experiments. Based on these results, evolutionarily acquired UNE-N elicits chemokine activities that would promote NRS-CCR3-mediated proinflammatory signaling in ILD.