PDBsum entry 5hdh

Immune system

PDB id: 5hdh

Contents

Protein chain

751 a.a.

Ligands

NAG-NAG-BMA-MAN

NAG-NAG

NAG-NAG-BMA-MAN-MAN

NAG ×6

SO4 ×3

MES

Waters ×79

PDB id:

5hdh

Name:

Immune system

Title:

Crystal structure of human tlr8 with an uncleaved z-loop

Structure:

Toll-like receptor 8. Chain: a. Fragment: unp residues 27-827. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: tlr8, unq249/pro286. Expressed in: drosophila. Expression_system_taxid: 7215

Resolution:

2.60Å R-factor: 0.208 R-free: 0.239

Authors:

H.Tanji,U.Ohto,T.Shimizu

Key ref:

H.Tanji et al. (2016). Autoinhibition and relief mechanism by the proteolytic processing of Toll-like receptor 8. Proc Natl Acad Sci U S A, 113, 3012-3017. PubMed id: 26929371 DOI: 10.1073/pnas.1516000113

Date:

05-Jan-16 Release date: 09-Mar-16

Protein chain

Q9NR97  (TLR8_HUMAN) -  Toll-like receptor 8 from Homo sapiens

Seq: 1041 a.a.

Struc: 751 a.a.

DOI no: 10.1073/pnas.1516000113

Proc Natl Acad Sci U S A 113:3012-3017 (2016)

PubMed id: 26929371

Autoinhibition and relief mechanism by the proteolytic processing of Toll-like receptor 8.

H.Tanji, U.Ohto, Y.Motoi, T.Shibata, K.Miyake, T.Shimizu.

ABSTRACT

Toll-like receptor 8 (TLR8) senses single-stranded RNA (ssRNA) and initiates innate immune responses. TLR8 requires proteolytic cleavage at the loop region (Z-loop) between leucine-rich repeat (LRR) 14 and LRR15 for its activation. However, the molecular basis of Z-loop processing remains unknown. To elucidate the mechanism of Z-loop processing, we performed biochemical and structural studies of how the Z-loop affects the function of TLR8. TLR8 with the uncleaved Z-loop is unable to form a dimer, which is essential for activation, irrespective of the presence of agonistic ligands. Crystallographic analysis revealed that the uncleaved Z-loop located on the ascending lateral face prevents the approach of the dimerization partner by steric hindrance. This autoinhibition mechanism of dimerization by the Z-loop might be occurring in the proteins of the same subfamily, TLR7 and TLR9.