6X0A

X-ray structure of a chimeric ParDE toxin-antitoxin complex from Mesorhizobium opportunistum

Summary for 6X0A

• Entry DOI: 10.2210/pdb6x0a/pdb
• Descriptor: Plasmid stabilization system, Putative addiction module antidote protein, CopG/Arc/MetJ family chimera, 1-ETHOXY-2-(2-ETHOXYETHOXY)ETHANE (3 entities in total)
• Functional Keywords: toxin-antitoxin complex, toxin
• Biological source: Mesorhizobium opportunistum (strain LMG 24607 / HAMBI 3007 / WSM2075); More
• Total number of polymer chains: 36
• Total formula weight: 401623.02

Authors

Lite, T.L.,Grant, R.A.,Laub, M.T. (deposition date: 2020-05-15, release date: 2020-11-25, Last modification date: 2023-10-18)

Primary citation

Lite, T.V.,Grant, R.A.,Nocedal, I.,Littlehale, M.L.,Guo, M.S.,Laub, M.T.
Uncovering the basis of protein-protein interaction specificity with a combinatorially complete library.
Elife, 9:-, 2020

PubMed Abstract: Protein-protein interaction specificity is often encoded at the primary sequence level. However, the contributions of individual residues to specificity are usually poorly understood and often obscured by mutational robustness, sequence degeneracy, and epistasis. Using bacterial toxin-antitoxin systems as a model, we screened a combinatorially complete library of antitoxin variants at three key positions against two toxins. This library enabled us to measure the effect of individual substitutions on specificity in hundreds of genetic backgrounds. These distributions allow inferences about the general nature of interface residues in promoting specificity. We find that positive and negative contributions to specificity are neither inherently coupled nor mutually exclusive. Further, a wild-type antitoxin appears optimized for specificity as no substitutions improve discrimination between cognate and non-cognate partners. By comparing crystal structures of paralogous complexes, we provide a rationale for our observations. Collectively, this work provides a generalizable approach to understanding the logic of molecular recognition.

PubMed: 33107822
DOI: 10.7554/eLife.60924

Experimental method

X-RAY DIFFRACTION (2.9 Å)