The aspartate-less receiver (ALR) domains: distribution, structure and function

PLoS Pathog. 2015 Apr 13;11(4):e1004795. doi: 10.1371/journal.ppat.1004795. eCollection 2015 Apr.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bacterial Physiological Phenomena*
  • Bacterial Proteins / metabolism*
  • Biological Evolution*
  • Computational Biology
  • Crystallography, X-Ray
  • Electrophoretic Mobility Shift Assay
  • Magnetic Resonance Spectroscopy
  • Streptococcus pneumoniae / metabolism

Substances

  • Bacterial Proteins

Associated data

  • PDB/4LZL