Specific high affinity interaction of Helicobacter pylori CagL with integrin α β promotes type IV secretion of CagA into human cells

buss-2019-25905.pdf1011 KB
Specific high affinity interaction of Helicobacter pylori CagL with integrin α β promotes type IV secretion of CagA into human cells

Date Published:

2019 Jun 14

Abstract:

CagL is an essential pilus surface component of the virulence-associated type IV secretion system (T4SS) employed by Helicobacter pylori to translocate the oncogenic effector protein CagA into human gastric epithelial cells. CagL contains an RGD motif and integrin α β is widely accepted as its host cell receptor. Here, we show that CagL binds integrin α β with substantially higher affinity and that this interaction is functionally important. Cell surface expression of α β on various cell lines correlated perfectly with cell adhesion to immobilized CagL and with binding of soluble CagL to cells. We found no such correlation for α β . The purified α β ectodomain bound CagL with high affinity. This interaction was highly specific, as the affinity of CagL for other RGD-binding integrins was two to three orders of magnitude weaker. Mutation of either conserved leucine in the CagL RGDLXXL motif, a motif that generally confers specificity for integrin α β and α β , lowered the affinity of CagL for α β . Stable expression of α β in α β -negative but α β -expressing human cells promoted two hallmarks of the functional H. pylori T4SS, namely translocation of CagA into host cells and induction of interleukin-8 secretion by host cells. These findings suggest that integrin α β , although not essential for T4SS function, represents an important host cell receptor for CagL.

Last updated on 07/01/2019