Novel structural and functional insights into the MoxR family of AAA+ ATPases
1Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
Abstract:
The MoxR family of AAA+ ATPases is widespread among bacteria and archaea, although their cellular functions are not well characterized. Based on recent studies, MoxR ATPases are proposed to have chaperone-like function for the maturation of specific protein complexes or for the insertion of cofactors into proteins. MoxR proteins have been found to be important modulators of multiple stress response pathways in different organisms. For example, the respective MoxR proteins have been found to play important roles in the cell envelope stress response in Rhizobium leguminosarum, in the oxidative stress, acid stress, and heat stress responses in Francisella tularensis, in the acid stress and stringent responses in Escherichia coli, in viral tail formation in the crenarchaeal Acidianus two-tailed virus, and in the utilization of carbon monoxide as the sole carbon source by the Gram-negative chemolithoautotrophe Oligotropha carboxidovorans. Recent structural studies on the MoxR proteins from E. coli and Cytophaga hutchinsonii show the unique spatial arrangement of the αβα and all-α subdomains of the AAA+ domain in these proteins compared to the typical arrangement found in canonical AAA+ proteins such as HslU. The spatial organization of the subdomains in the AAA+ domain of MoxR proteins is similar to that found in the ATPase component of the magnesium chelatase complexes, possibly suggesting a similar mechanism of function. In this review, we provide an overview of the newly identified functions and the newly obtained structures of MoxR AAA+ ATPases.
Insights
MoxR ATPases, widespread in microbes, are newly found to modulate stress responses and aid protein complex maturation. Their unique AAA+ domain structure resembles magnesium chelatase, suggesting novel functions.
Area of Science:
- Microbiology
- Biochemistry
- Structural Biology
Background:
- MoxR family of ATPases are conserved in bacteria and archaea.
- Cellular functions of MoxR ATPases are not well understood.
- Proposed roles include chaperone-like functions and cofactor insertion.
Purpose of the Study:
- To review newly identified functions of MoxR ATPases.
- To present recent structural insights into MoxR proteins.
- To explore the implications of MoxR structure for function.
Main Methods:
- Literature review of recent studies on MoxR ATPases.
- Analysis of structural data from X-ray crystallography or cryo-EM.
- Comparative analysis with other AAA+ proteins and related complexes.
Main Results:
- MoxR proteins modulate diverse stress responses (oxidative, acid, heat) and metabolic pathways (CO utilization).
- Structural studies reveal unique AAA+ domain organization in MoxR proteins.
- This organization is similar to the ATPase component of magnesium chelatase complexes.
Conclusions:
- MoxR ATPases play critical roles in microbial stress adaptation and complex assembly.
- The unique structure suggests a conserved or related mechanism of action.
- Further research into MoxR function and structure is warranted.
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