4YKA

The structure of Agrobacterium tumefaciens ClpS2 in complex with L-tyrosinamide

Summary for 4YKA

• Entry DOI: 10.2210/pdb4yka/pdb
• Related: 4YJM 4YJX
• Descriptor: ATP-dependent Clp protease adapter protein ClpS 2, SULFATE ION, L-TYROSINAMIDE, ... (4 entities in total)
• Functional Keywords: n-end rule, protease adaptor, protein binding
• Biological source: Agrobacterium fabrum (strain C58 / ATCC 33970)
• Total number of polymer chains: 4
• Total formula weight: 47843.76

Authors

Stein, B.,Grant, R.A.,Sauer, R.T.,Baker, T.A. (deposition date: 2015-03-04, release date: 2016-01-27, Last modification date: 2023-09-27)

Primary citation

Stein, B.J.,Grant, R.A.,Sauer, R.T.,Baker, T.A.
Structural Basis of an N-Degron Adaptor with More Stringent Specificity.
Structure, 24:232-242, 2016

PubMed Abstract: The N-end rule dictates that a protein's N-terminal residue determines its half-life. In bacteria, the ClpS adaptor mediates N-end-rule degradation, by recognizing proteins bearing specific N-terminal residues and delivering them to the ClpAP AAA+ protease. Unlike most bacterial clades, many α-proteobacteria encode two ClpS paralogs, ClpS1 and ClpS2. Here, we demonstrate that both ClpS1 and ClpS2 from A. tumefaciens deliver N-end-rule substrates to ClpA, but ClpS2 has more stringent binding specificity, recognizing only a subset of the canonical bacterial N-end-rule residues. The basis of this enhanced specificity is addressed by crystal structures of ClpS2, with and without ligand, and structure-guided mutagenesis, revealing protein conformational changes and remodeling in the substrate-binding pocket. We find that ClpS1 and ClpS2 are differentially expressed during growth in A. tumefaciens and conclude that the use of multiple ClpS paralogs allows fine-tuning of N-end-rule degradation at the level of substrate recognition.

PubMed: 26805523
DOI: 10.1016/j.str.2015.12.008

Experimental method

X-RAY DIFFRACTION (2.801 Å)