5HDH

Crystal structure of human TLR8 with an uncleaved Z-loop

Summary for 5HDH

• Entry DOI: 10.2210/pdb5hdh/pdb
• Descriptor: Toll-like receptor 8, alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: immune system, tlr8, innate immunity, proteolytic cleavage
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 95302.10

Authors

Tanji, H.,Ohto, U.,Shimizu, T. (deposition date: 2016-01-05, release date: 2016-03-09, Last modification date: 2024-10-30)

Primary citation

Tanji, H.,Ohto, U.,Motoi, Y.,Shibata, T.,Miyake, K.,Shimizu, T.
Autoinhibition and relief mechanism by the proteolytic processing of Toll-like receptor 8
Proc.Natl.Acad.Sci.USA, 113:3012-3017, 2016

PubMed 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.

PubMed: 26929371
DOI: 10.1073/pnas.1516000113

Experimental method

X-RAY DIFFRACTION (2.6 Å)