PDBsum entry 2lnh

Signaling protein/protein binding

PDB id: 2lnh

Contents

Protein chains

65 a.a.

67 a.a.

47 a.a.

PDB id:

2lnh

Name:

Signaling protein/protein binding

Title:

Enterohaemorrhagic e. Coli (ehec) exploits a tryptophan switch to hijack host f-actin assembly

Structure:

Neural wiskott-aldrich syndrome protein. Chain: a. Fragment: unp residues 207-270. Synonym: n-wasp. Engineered: yes. Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1. Chain: b. Fragment: sh3 domain residues 339-402.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: wasl. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: baiap2l1, irtks. Escherichia coli o157:h7. Organism_taxid: 83334.

NMR struc:

20 models

Authors:

O.Aitio,M.Hellman,B.Skehan,T.Kesti,J.M.Leong,K.Saksela,P.Permi

Key ref:

O.Aitio et al. (2012). Enterohaemorrhagic Escherichia coli exploits a tryptophan switch to hijack host f-actin assembly. Structure, 20, 1692-1703. PubMed id: 22921828

Date:

28-Dec-11 Release date: 29-Aug-12

Protein chain

O00401  (WASL_HUMAN) -  Actin nucleation-promoting factor WASL from Homo sapiens

Seq: 505 a.a.

Struc: 65 a.a.*

Protein chain

Q9UHR4  (BI2L1_HUMAN) -  BAR/IMD domain-containing adapter protein 2-like 1 from Homo sapiens

Seq: 511 a.a.

Struc: 67 a.a.*

Protein chain

P0DJ89  (ESFU3_ECO57) -  Secreted effector protein EspF(U) from Escherichia coli O157:H7

Seq: 337 a.a.

Struc: 47 a.a.

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Structure 20:1692-1703 (2012)

PubMed id: 22921828

Enterohaemorrhagic Escherichia coli exploits a tryptophan switch to hijack host f-actin assembly.

O.Aitio, M.Hellman, B.Skehan, T.Kesti, J.M.Leong, K.Saksela, P.Permi.

ABSTRACT

Intrinsically disordered protein (IDP)-mediated interactions are often characterized by low affinity but high specificity. These traits are essential in signaling and regulation that require reversibility. Enterohaemorrhagic Escherichia coli (EHEC) exploit this situation by commandeering host cytoskeletal signaling to stimulate actin assembly beneath bound bacteria, generating "pedestals" that promote intestinal colonization. EHEC translocates two proteins, EspF(U) and Tir, which form a complex with the host protein IRTKS. The interaction of this complex with N-WASP triggers localized actin polymerization. We show that EspF(U) is an IDP that contains a transiently α-helical N-terminus and dynamic C-terminus. Our structure shows that single EspF(U) repeat forms a high-affinity trimolecular complex with N-WASP and IRTKS. We demonstrate that bacterial and cellular ligands interact with IRTKS SH3 in a similar fashion, but the bacterial protein has evolved to outcompete cellular targets by utilizing a tryptophan switch that offers superior binding affinity enabling EHEC-induced pedestal formation.