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The aspartate-less receiver (ALR) domains: distribution, structure and function. PLoS Pathog 2015 Apr;11(4):e1004795 PMID: 25875291 PMCID: PMC4395418

Abstract

Two-component signaling systems are ubiquitous in bacteria, Archaea and plants and play important roles in sensing and responding to environmental stimuli. To propagate a signaling response the typical system employs a sensory histidine kinase that phosphorylates a Receiver (REC) domain on a conserved aspartate (Asp) residue. Although it is known that some REC domains are missing this Asp residue, it remains unclear as to how many of these divergent REC domains exist, what their functional roles are and how they are regulated in the absence of the conserved Asp. Here we have compiled all deposited REC domains missing their phosphorylatable Asp residue, renamed here as the Aspartate-Less Receiver (ALR) domains. Our data show that ALRs are surprisingly common and are enriched for when attached to more rare effector outputs. Analysis of our informatics and the available ALR atomic structures, combined with structural, biochemical and genetic data of the ALR archetype RitR from Streptococcus pneumoniae presented here suggest that ALRs have reorganized their active pockets to instead take on a constitutive regulatory role or accommodate input signals other than Asp phosphorylation, while largely retaining the canonical post-phosphorylation mechanisms and dimeric interface. This work defines ALRs as an atypical REC subclass and provides insights into shared mechanisms of activation between ALR and REC domains.

Author List

Maule AF, Wright DP, Weiner JJ, Han L, Peterson FC, Volkman BF, Silvaggi NR, Ulijasz AT

Authors

Francis C. Peterson PhD Professor in the Biochemistry department at Medical College of Wisconsin
Nicholas R. Silvaggi PhD Assistant Professor in the Chemistry and Biochemistry department at University of Wisconsin - Milwaukee
Brian F. Volkman PhD Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Bacterial Proteins
Computational Biology
Crystallography, X-Ray
Electrophoretic Mobility Shift Assay
Magnetic Resonance Spectroscopy
Streptococcus pneumoniae



View this publication's entry at the Pubmed website PMID: 25875291
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