9xuz | pdb_00009xuz
Solution structure of Site2 dimer of Ler
Structural highlights
Publication Abstract from PubMedThe locus of enterocyte effacement-encoded regulator (Ler) is a master transcriptional activator essential for the virulence of enterohemorrhagic and enteropathogenic Escherichia coli. Although Ler shares homology with the global silencer H-NS, it functions uniquely as an anti-silencer, a role strictly dependent on its oligomerization state. However, the structural mechanism governing Ler assembly remains poorly understood. In this study, we have characterized the N-terminal oligomerization domain (Ler(1-74)) of Ler using solution NMR spectroscopy and biophysical assays, and found that Ler(1-74) shows concentration-dependent oligomerization. We demonstrate that Ler oligomerization is driven by two distinct interfaces with contrasting dynamic properties. We determined the solution structure of the Ler(18-74) dimer, revealing a stable, anti-parallel "tail-to-tail" interface (dimer Site-2, residues 35-66) stabilized by a hydrophobic core. In contrast, the N-terminal interface (dimer Site-1, residues 12-33) forms a highly dynamic "head-to-head" dimer, which undergoes significant conformational exchange and exhibits concentration- and temperature-dependent dimerization. Based on these findings, we propose a structural model wherein Ler forms supramolecular assemblies through the propagation of alternating stable (Site-2) and dynamic (Site-1) interactions. This architecture, while reminiscent of H-NS, displays distinct stability features that may underlie Ler's specific anti-silencing function in bacterial pathogenesis. Structural basis of the oligomerization of anti-silencer Ler from enterohemorrhagic E. coli (EHEC).,Wang G, Duan B, Xia B Struct Dyn. 2026 Apr 14;13(2):024702. doi: 10.1063/4.0001203. eCollection 2026 , Mar. PMID:41987883[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||
