A major invasion

The food-borne pathogen Listeria monocytogenes enters human cells by interacting with the host-cell receptor E-cadherin using internalin (InIA), a major invasion protein. This results in the bacteria being phagocytosed by cells — such as intestinal epithelial cells — that are usually non-phagocytic. Now, in Cell, Heinz and colleagues provide new insights into this interaction. They present the crystal structures of the functional domain of InIA (InIA′) alone and in complex with the amino-terminal immunoglobulin-like domain from human E-cadherin (hEC1).

The authors found that InIA′ forms an extended, sickle-shaped structure, and that hEC1 specifically binds to and fills the central cleft that is formed by the curved leucine-rich repeats (LRRs) of InIA′. LRRs are usually quite rigid, but a hinge region in LRR6 of InIA′ provides the flexibility needed to form the InIA′–hEC1 complex.

The Pro16 residue of hEC1 is important for the recognition of human E-cadherin by InIA, and in mice, where Pro16 is replaced by glutamate, InIA does not bind epithelia. Consistent with this, the authors confirmed that Pro16 is essential for the InIA′–hEC1 interaction using structural and mutagenesis studies. Their work has therefore provided “...a detailed picture of the first steps leading to human infection by L. monocytogenes”, insights into “...the structural basis for host tropism”, and the possibility of new therapeutic approaches. REFERENCE Schubert, W. D. et al. Structure of internalin, a major invasion protein of Listeria monocytogenes, in complex with its human receptor E-cadherin. Cell 111, 825–836 (2002)

Dimension difficulties

Protein synthesis on a ribosome is terminated when a stop codon enters the decoding centre (DC) of the 30S ribosomal subunit and is recognized by a class-I release factor (RF). A conserved motif in RFs (SPF in RF2) is thought to interact directly with the stop codon in the DC, and the GGQ motif of RFs is then thought to interact with the peptidyl-transferase centre (PTC) of the 50S ribosomal subunit to stimulate peptide release. There is, however, a problem with this model — the distance between the DC and PTC is ∼73 Å and, in the X-ray structure of RF2, the SPF and GGQ motifs are only 23 Å apart.

Two studies in Nature — from Frank and colleagues and van Heel and co-workers — now give us the solution to this dimension difficulty. Both groups used cryo-electron microscopy to study the structure of the bacterial RF2–ribosome complex at ∼10–14-Å resolution. They found that RF2 has an open conformation when bound to ribosomes, which allows it to span the distance between the DC and the PTC. The authors therefore propose a model in which stop-codon recognition by the RF2 SPF motif causes a structural change that converts RF2 from a compact to an open conformation, which places its GGQ motif near the PTC. In addition, the authors showed that RF2 mimics transfer RNAs functionally, and not structurally as was previously thought. REFERENCE Rawat, U. B. S. et al. A cryo-electron microscopic study of ribosome-bound termination factor RF2. Nature 421, 87–90 (2003) Klaholz, B. P. et al. Structure of the Escherichia coli ribosomal termination complex with release factor 2. Nature 421, 90–94 (2003)