Crystal Structure of Invasin: A Bacterial Integrin-Binding Protein

Abstract

The Yersinia pseudotuberculosis invasin protein promotes bacterial entry by binding to host cell integrins with higher affinity than natural substrates such as fibronectin. The 2.3 angstrom crystal structure of the invasin extracellular region reveals five domains that form a 180 angstrom rod with structural similarities to tandem fibronectin type III domains. The integrin-binding surfaces of invasin and fibronectin include similarly located key residues, but in the context of different folds and surface shapes. The structures of invasin and fibronectin provide an example of convergent evolution, in which invasin presents an optimized surface for integrin binding, in comparison with host substrates.

Cell Surface-localized Nucleolin Is a Eukaryotic Receptor for the Adhesin Intimin-γ of Enterohemorrhagic Escherichia coliO157:H7

“…The host cell binding domain of intimin-␣ is structurally similar to invasin despite little sequence similarity (34,60,61). The structure of intimin-␥ has not been solved; however, based on sequence similarities between intimin-␣ and intimin-␥, we assume that intimin-␥ also shares a similar conformation.…”

Crystal Structure of the N-terminal Domain of the Group B Streptococcus Alpha C Protein

“…Invasin from Yersinia pseudotuberculosis (Inv497) is a non-RGD protein that competes with FnIII by binding to ␣ 5 ␤ 1 integrin at the same site as fibronectin (51-53) with ϳ100 times greater affinity. In reporting the invasin structure, Hamburger et al (51) proposed that Inv497 (PDB code 1cwv), although structurally dissimilar from FnIII, shares with FnIII a structurally conserved triangular arrangement of charged residues (Fig. 7, A and B).…”

“…Residues (RG)Asp 1495 (D1495), Asp 1373 (D1373), and Arg 1379 (D1379) of FnIII are known to be required for integrin binding (35,40,50). Residues Asp 911 (D911) and Asp 811 (D811) of Yersinia Inv497 are known to be involved in integrin binding (54 -56,71) and residue Arg 883 (R883) has been proposed as a structural analogue of Arg 1379 (R1379) of FnIII based on interresidue distances (51).…”

“…7, A and B). The proposed integrin-binding triangle in Inv497 includes Asp 911 and Asp 811 , which were identified by mutational analysis (54 -56), and Arg 883 , which was suggested by structural considerations (51).…”

“…7. A structurally conserved triangle of exposed charges may be implicated in integrin binding. Ribbon representations of FnIII9 -10 (A) (35), Inv497 D4-D5 (B) (51), and domain 1 of NtACP (C) (this paper). Distances reported are measured between C ␣ .…”