Structural basis of adaptor-mediated protein degradation by the tail-specific PDZ-protease Prc

Ming Yuan Su, Nilanjan Som, Chia Yun Wu, Shih Chieh Su, Yi Ting Kuo, Lu Chu Ke, Meng Ru Ho, Shiou Ru Tzeng, Ching Hao Teng, Dominique Mengin-Lecreulx, Manjula Reddy, Chung I. Chang

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Peptidoglycan (PG) is a highly cross-linked, protective mesh-like sacculus that surrounds the bacterial cytoplasmic membrane. Expansion of PG is tightly coupled to growth of a bacterial cell and requires hydrolases to cleave the cross-links for insertion of nascent PG material. In Escherichia coli, a proteolytic system comprising the periplasmic PDZ-protease Prc and the lipoprotein adaptor NlpI contributes to PG enlargement by regulating cellular levels of MepS, a cross-link-specific hydrolase. Here, we demonstrate how NlpI binds Prc to facilitate the degradation of its substrate MepS by structural and mutational analyses. An NlpI homodimer binds two molecules of Prc and forms three-sided MepS-docking cradles using its tetratricopeptide repeats. Prc forms a monomeric bowl-shaped structure with a lid-like PDZ domain connected by a substrate-sensing hinge that recognizes the bound C terminus of the substrate. In summary, our study reveals mechanistic details of protein degradation by the PDZ-protease Prc bound to its cognate adaptor protein.

Original languageEnglish
Article number1516
JournalNature communications
Volume8
Issue number1
DOIs
Publication statusPublished - 2017 Dec 1

Fingerprint

protease
Peptidoglycan
Proteolysis
Peptide Hydrolases
degradation
proteins
Degradation
Hydrolases
lipoproteins
Proteins
Substrates
hinges
Escherichia
PDZ Domains
insertion
mesh
Hinges
Escherichia coli
Lipoproteins
membranes

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Su, M. Y., Som, N., Wu, C. Y., Su, S. C., Kuo, Y. T., Ke, L. C., ... Chang, C. I. (2017). Structural basis of adaptor-mediated protein degradation by the tail-specific PDZ-protease Prc. Nature communications, 8(1), [1516]. https://doi.org/10.1038/s41467-017-01697-9
Su, Ming Yuan ; Som, Nilanjan ; Wu, Chia Yun ; Su, Shih Chieh ; Kuo, Yi Ting ; Ke, Lu Chu ; Ho, Meng Ru ; Tzeng, Shiou Ru ; Teng, Ching Hao ; Mengin-Lecreulx, Dominique ; Reddy, Manjula ; Chang, Chung I. / Structural basis of adaptor-mediated protein degradation by the tail-specific PDZ-protease Prc. In: Nature communications. 2017 ; Vol. 8, No. 1.
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abstract = "Peptidoglycan (PG) is a highly cross-linked, protective mesh-like sacculus that surrounds the bacterial cytoplasmic membrane. Expansion of PG is tightly coupled to growth of a bacterial cell and requires hydrolases to cleave the cross-links for insertion of nascent PG material. In Escherichia coli, a proteolytic system comprising the periplasmic PDZ-protease Prc and the lipoprotein adaptor NlpI contributes to PG enlargement by regulating cellular levels of MepS, a cross-link-specific hydrolase. Here, we demonstrate how NlpI binds Prc to facilitate the degradation of its substrate MepS by structural and mutational analyses. An NlpI homodimer binds two molecules of Prc and forms three-sided MepS-docking cradles using its tetratricopeptide repeats. Prc forms a monomeric bowl-shaped structure with a lid-like PDZ domain connected by a substrate-sensing hinge that recognizes the bound C terminus of the substrate. In summary, our study reveals mechanistic details of protein degradation by the PDZ-protease Prc bound to its cognate adaptor protein.",
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Su, MY, Som, N, Wu, CY, Su, SC, Kuo, YT, Ke, LC, Ho, MR, Tzeng, SR, Teng, CH, Mengin-Lecreulx, D, Reddy, M & Chang, CI 2017, 'Structural basis of adaptor-mediated protein degradation by the tail-specific PDZ-protease Prc', Nature communications, vol. 8, no. 1, 1516. https://doi.org/10.1038/s41467-017-01697-9

Structural basis of adaptor-mediated protein degradation by the tail-specific PDZ-protease Prc. / Su, Ming Yuan; Som, Nilanjan; Wu, Chia Yun; Su, Shih Chieh; Kuo, Yi Ting; Ke, Lu Chu; Ho, Meng Ru; Tzeng, Shiou Ru; Teng, Ching Hao; Mengin-Lecreulx, Dominique; Reddy, Manjula; Chang, Chung I.

In: Nature communications, Vol. 8, No. 1, 1516, 01.12.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Structural basis of adaptor-mediated protein degradation by the tail-specific PDZ-protease Prc

AU - Su, Ming Yuan

AU - Som, Nilanjan

AU - Wu, Chia Yun

AU - Su, Shih Chieh

AU - Kuo, Yi Ting

AU - Ke, Lu Chu

AU - Ho, Meng Ru

AU - Tzeng, Shiou Ru

AU - Teng, Ching Hao

AU - Mengin-Lecreulx, Dominique

AU - Reddy, Manjula

AU - Chang, Chung I.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Peptidoglycan (PG) is a highly cross-linked, protective mesh-like sacculus that surrounds the bacterial cytoplasmic membrane. Expansion of PG is tightly coupled to growth of a bacterial cell and requires hydrolases to cleave the cross-links for insertion of nascent PG material. In Escherichia coli, a proteolytic system comprising the periplasmic PDZ-protease Prc and the lipoprotein adaptor NlpI contributes to PG enlargement by regulating cellular levels of MepS, a cross-link-specific hydrolase. Here, we demonstrate how NlpI binds Prc to facilitate the degradation of its substrate MepS by structural and mutational analyses. An NlpI homodimer binds two molecules of Prc and forms three-sided MepS-docking cradles using its tetratricopeptide repeats. Prc forms a monomeric bowl-shaped structure with a lid-like PDZ domain connected by a substrate-sensing hinge that recognizes the bound C terminus of the substrate. In summary, our study reveals mechanistic details of protein degradation by the PDZ-protease Prc bound to its cognate adaptor protein.

AB - Peptidoglycan (PG) is a highly cross-linked, protective mesh-like sacculus that surrounds the bacterial cytoplasmic membrane. Expansion of PG is tightly coupled to growth of a bacterial cell and requires hydrolases to cleave the cross-links for insertion of nascent PG material. In Escherichia coli, a proteolytic system comprising the periplasmic PDZ-protease Prc and the lipoprotein adaptor NlpI contributes to PG enlargement by regulating cellular levels of MepS, a cross-link-specific hydrolase. Here, we demonstrate how NlpI binds Prc to facilitate the degradation of its substrate MepS by structural and mutational analyses. An NlpI homodimer binds two molecules of Prc and forms three-sided MepS-docking cradles using its tetratricopeptide repeats. Prc forms a monomeric bowl-shaped structure with a lid-like PDZ domain connected by a substrate-sensing hinge that recognizes the bound C terminus of the substrate. In summary, our study reveals mechanistic details of protein degradation by the PDZ-protease Prc bound to its cognate adaptor protein.

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