6LX0

Structure of Leptospira santarosai serovar shermani LRR protein LSS11580

Summary for 6LX0

• Entry DOI: 10.2210/pdb6lx0/pdb
• Descriptor: Membrane protein (2 entities in total)
• Functional Keywords: leptospira, leptospirosis, leucine-rich repeat, cell adhesion, membrane protein, unknown function
• Biological source: Leptospira santarosai serovar Shermani str. LT 821
• Total number of polymer chains: 1
• Total formula weight: 24581.54

Authors

Chu, C.H.,Hsu, S.H.,Yang, C.W.,Sun, Y.J. (deposition date: 2020-02-10, release date: 2020-12-23, Last modification date: 2023-11-29)

Primary citation

Hsu, S.H.,Chu, C.H.,Tian, Y.C.,Chang, M.Y.,Chou, L.F.,Sun, Y.J.,Yang, C.W.
Crystal structure of Leptospira leucine-rich repeat 20 reveals a novel E-cadherin binding protein to induce NGAL expression in HK2 cells.
Biochem.J., 477:4313-4326, 2020

PubMed Abstract: Leptospirosis is the most common zoonotic disease caused by pathogenic Leptospira, which is classified into three groups according to virulence. Its pathogenic and intermediate species contain leucine-rich repeat (LRR) proteins that are rarely expressed in non-pathogenic strains. In this study, we presented the crystal structure of LSS_11580 (rLRR20) from pathogenic L. santarosai serovar Shermani. X-ray diffraction at a resolution of 1.99 Å revealed a horseshoe-shaped structure containing seven α-helices and five β-sheets. Affinity assays indicated that rLRR20 interacts with E-cadherin on the cell surface. Interestingly, its binds to the extracellular (EC) 1 domain in human epithelial (E)-cadherin, which is responsible for binding to another E-cadherin molecule in neighboring cells. Several charged residues on the concave face of LRR20 were predicted to interact with EC1 domain. In the affinity assays, these charged residues were replaced by alanine, and their affinities to E-cadherin were measured. Three vital residues and mutation variants of LRR20, namely D56A, E59A, and E123A, demonstrated significantly reduced affinity to E-cadherin compared with the control. Besides, we also demonstrated that rLRR20 induced the expression of neutrophil gelatinase-associated lipocalin (NGAL) in HK2 cells. The low ability of the three mutation variants to induce NGAL expression further demonstrates this induction. The present findings indicate that LRR20 from pathogenic Leptospira binds to E-cadherin and interacts with its EC1 domain. In addition, its induction of NGAL expression in HK2 cells is associated with acute kidney injury in human.

PubMed: 33094809
DOI: 10.1042/BCJ20200547

Experimental method

X-RAY DIFFRACTION (1.99 Å)