Crystal structure of pentapeptide-independent chemotaxis receptor methyltransferase (CheR) reveals idiosyncratic structural determinants for receptor recognition

Batra, Monu; Sharma, Rajesh; Malik, Anjali; Dhindwal, Sonali; Kumar, Pravindra; Tomar, Shailly

doi:10.1016/j.jsb.2016.08.005

Cited by 9 publications

(11 citation statements)

References 66 publications

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“…Based on the studies on other chemotaxis methyltransferases (22,23), the C-terminal domain and the domain linker are likely involved in the binding of the cofactor AdoMet. In the free CheR1 structure, an AdoMet-binding pocket can be readily identified by overlaying the structure with that of the S-adenosyl-L-homocysteine (SAH)-bound BsCheR (Protein Data Bank code 5FTW; Fig.…”

Section: Binding Of Mapz To Cher1 Resulting In Disruption Of the S-admentioning

confidence: 99%

“…1C). The ␤-subdomain, which is inserted between ␣7 and ␣10, is unique to chemotaxis methyltransferases (21)(22)(23) (Fig. S3).…”

Section: Overall Structure Of the Mapz-c-di-gmp-cher1 Ternary Complexmentioning

confidence: 99%

“…The only noticeable direct polar interaction that involves ␣2 seems to be the hydrogen bond formed between Glu 109 (␣2) and Ser 146 (CheR1). Apart from the residues in ␣1 and ␣2, the main chain groups of Leu 92 and Ile 90 from the loop prior to ␣1 form three hydrogen bonds with Val 22 and Gly 20 of CheR1 (Fig. 2C), whereas His 123 and Asp 124 from the loop downstream of ␣2 interact with Thr 18 and Arg 62 of CheR1 through a hydrogen bond and salt bridge, respectively.…”

Section: Pilz Adaptor-mediated C-di-gmp Signalingmentioning

confidence: 99%

“…C, specific interactions involving residues from the non-C-terminal regions of MapZ. The N-terminal ␤1-␤2 loop and ␤6-␤7 loop in MapZ contact the C-terminal domain of CheR1, and the loop residues Ile 90 and Leu 92 between ␤8 and ␣1 engage in hydrogen-bonding interactions with the N-terminal loop (␣1-␣2) residues Gly 20 and Val22 in CheR1. For clarity, the residues Asp 93 and Ser 96 from ␣1 of MapZ interacting with Lys27 and Arg34 of CheR1 are shown in this panel instead of in A.…”

mentioning

confidence: 99%

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Structural analyses unravel the molecular mechanism of cyclic di-GMP regulation of bacterial chemotaxis via a PilZ adaptor protein

Yan

Xin

Yen

et al. 2018

Journal of Biological Chemistry

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The bacterial second messenger cyclic di-GMP (c-di-GMP) has emerged as a prominent mediator of bacterial physiology, motility, and pathogenicity. c-di-GMP often regulates the function of its protein targets through a unique mechanism that involves a discrete PilZ adaptor protein. However, the molecular mechanism for PilZ protein-mediated protein regulation is unclear. Here, we present the structure of the PilZ adaptor protein MapZ cocrystallized in complex with c-di-GMP and its protein target CheR1, a chemotaxis-regulating methyltransferase in This cocrystal structure, together with the structure of free CheR1, revealed that the binding of c-di-GMP induces dramatic structural changes in MapZ that are crucial for CheR1 binding. Importantly, we found that restructuring and repositioning of two C-terminal helices enable MapZ to disrupt the CheR1 active site by dislodging a structural domain. The crystallographic observations are reinforced by protein-protein binding and single cell-based flagellar motor switching analyses. Our studies further suggest that the regulation of chemotaxis by c-di-GMP through MapZ orthologs/homologs is widespread in proteobacteria and that the use of allosterically regulated C-terminal motifs could be a common mechanism for PilZ adaptor proteins. Together, the findings provide detailed structural insights into how c-di-GMP controls the activity of an enzyme target indirectly through a PilZ adaptor protein.

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Section: Binding Of Mapz To Cher1 Resulting In Disruption Of the S-admentioning

confidence: 99%

“…1C). The ␤-subdomain, which is inserted between ␣7 and ␣10, is unique to chemotaxis methyltransferases (21)(22)(23) (Fig. S3).…”

Section: Overall Structure Of the Mapz-c-di-gmp-cher1 Ternary Complexmentioning

confidence: 99%

Section: Pilz Adaptor-mediated C-di-gmp Signalingmentioning

confidence: 99%

mentioning

confidence: 99%

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Structural analyses unravel the molecular mechanism of cyclic di-GMP regulation of bacterial chemotaxis via a PilZ adaptor protein

Yan

Xin

Yen

et al. 2018

Journal of Biological Chemistry

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“…In order to decipher the mechanism by which the inhibition of CheR1 by MapZ is enhanced by c-di-GMP, we determined crystal structures of CheR1 with SAH and of CheR1 in complex with MapZ and c-di-GMP. Structures of CheR from S. typhimurium and Bacillus subtilis have been solved and this is the third structure of CheR (Djordjevic & Stock, 1998;Batra et al, 2016). Our structures indicate that binding of c-di-GMP to MapZ makes it easier for MapZ to bind CheR1, which blocks the active pocket of CheR1 and thus inhibits the methylation reaction.…”

Section: Introductionmentioning

confidence: 85%

Structural basis for the regulation of chemotaxis by MapZ in the presence of c-di-GMP

Zhu

Yuan

2017

Acta Crystallogr D Struct Biol

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The bacterial second messenger cyclic diguanylate monophosphate (c-di-GMP) mediates multiple aspects of bacterial physiology through binding to various effectors. In some cases, these effectors are single-domain proteins which only contain a PilZ domain. It remains largely unknown how single-domain PilZ proteins function and regulate their downstream targets. Recently, a single-domain PilZ protein, MapZ (PA4608), was identified to inhibit the activity of the methyltransferase CheR1. Here, crystal structures of the C-terminal domain of CheR1 containing SAH and of CheR1 in complex with c-di-GMP-bound MapZ are reported. It was observed that the binding site of MapZ in CheR1 partially overlaps with the SAH/SAM-binding pocket. Consequently, binding of MapZ blocks SAH/SAM binding. This provides direct structural evidence on the mechanism of inhibition of CheR1 by MapZ in the presence of c-di-GMP.

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Chemoreceptors with C-terminal pentapeptides for CheR and CheB binding are abundant in bacteria that maintain host interactions

Ortega

Krell

2020

Computational and Structural Biotechnology Journal

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Crystal structure of pentapeptide-independent chemotaxis receptor methyltransferase (CheR) reveals idiosyncratic structural determinants for receptor recognition

Cited by 9 publications

References 66 publications

Structural analyses unravel the molecular mechanism of cyclic di-GMP regulation of bacterial chemotaxis via a PilZ adaptor protein

Structural analyses unravel the molecular mechanism of cyclic di-GMP regulation of bacterial chemotaxis via a PilZ adaptor protein

Structural basis for the regulation of chemotaxis by MapZ in the presence of c-di-GMP

Chemoreceptors with C-terminal pentapeptides for CheR and CheB binding are abundant in bacteria that maintain host interactions

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