DRG2

Last update 23 Jan 2025

Basic Info

Synonyms

developmentally regulated GTP binding protein 2, Developmentally-regulated GTP-binding protein 2, DRG-2

+ [3]

Introduction

Catalyzes the conversion of GTP to GDP through hydrolysis of the gamma-phosphate bond in GTP. When hydroxylated at C-3 of 'Lys-21' by JMJD7, may bind to RNA and play a role in translation.

100 Clinical Results associated with DRG2

100 Translational Medicine associated with DRG2

0 Patents (Medical) associated with DRG2

Literatures (Medical) associated with DRG2

01 Nov 2024·Structure

Rewiring protein binding specificity in paralogous DRG/DFRP complexes

Article

Author: Coleman, Mathew L ; Westrip, Christian A E ; Westrip, Christian A.E. ; Smerdon, Stephen J ; Coleman, Mathew L. ; Smerdon, Stephen J.

Eukaryotes have two paralogous developmentally regulated GTP-binding (DRG) proteins: DRG1 and DRG2, both of which have a conserved binding partner called DRG family regulatory protein 1 and 2 (DFRP1 and DFRP2), respectively. DFRPs are important for the function of DRGs and interact with their respective DRG via a conserved region called the DFRP domain. Despite being highly similar, DRG1 and DRG2 have strict binding specificity for their respective DFRP. Using AlphaFold generated structure models of the human DRG/DFRP complexes, we have biochemically characterized their interactions and identified interface residues involved in determining specificity. This analysis revealed that as few as five mutations in DRG1 can switch binding from DFRP1 to DFRP2. Moreover, while DFRP1 binding confers increased stability and GTPase activity to DRG1, DFRP2 binding only supports increased stability. Overall, this work provides new insight into the structural determinants responsible for the binding specificities of the DRG/DFRP complexes.

01 Dec 2023·Clinical Immunology

DRG2 in macrophages is crucial for initial inflammatory response and protection against Listeria monocytogenes infection

Article

Author: Lee, Sang Chul ; Cho, Wha Ja ; Ju, Seong A ; Ahn, Byungyong ; Park, Jeong Woo ; Yi, Jawoon ; Kim, Byung Sam ; Won, Young-Wook ; Lee, Unn Hwa ; Park, Sang Jin ; Han, In Seob ; Park, Jihwan ; Lee, Byung Ju

Innate immune response is critical for the control of Listeria monocytogenes infection. Here, we identified developmentally regulated GTP-binding protein 2 (DRG2) in macrophages as a major regulator of the innate immune response against L. monocytogenes infection. Both whole-body DRG2 knockout (KO) mice and macrophage-specific DRG2 KO mice had low levels of IL-6 during early infection and increased susceptibility to L. monocytogenes infection. Following an initial impaired inflammatory response of macrophages upon i.p. L. monocytogenes infection, DRG2^-/- mice showed delayed recruitment of neutrophils and monocytes into the peritoneal cavity, which led to elevated bacterial burden, inflammatory cytokine production at a late infection time point, and liver micro-abscesses. DRG2 deficiency decreased the transcriptional activity of NF-κB and impaired the inflammatory response of both bone marrow-derived and peritoneal macrophages upon L. monocytogenes stimulation. Our findings reveal that DRG2 in macrophages is critical for the initial inflammatory response and protection against L. monocytogenes infection.

01 Dec 2021·Cellular and Molecular Life SciencesQ2 · BIOLOGY

Developmentally regulated GTPases: structure, function and roles in disease

Q2 · BIOLOGY

Review

Author: Zhuang, Qinqin ; Eaton, Charlotte D ; Westrip, Christian A E ; Coleman, Mathew L ; Hall, Charlotte

AbstractGTPases are a large superfamily of evolutionarily conserved proteins involved in a variety of fundamental cellular processes. The developmentally regulated GTP-binding protein (DRG) subfamily of GTPases consists of two highly conserved paralogs,DRG1andDRG2, both of which have been implicated in the regulation of cell proliferation, translation and microtubules. Furthermore, DRG1 and 2 proteins both have a conserved binding partner, DRG family regulatory protein 1 and 2 (DFRP1 and DFRP2), respectively, that prevents them from being degraded. Similar to DRGs, the DFRP proteins have also been studied in the context of cell growth control and translation. Despite these proteins having been implicated in several fundamental cellular processes they remain relatively poorly characterized, however. In this review, we provide an overview of the structural biology and biochemistry of DRG GTPases and discuss current understanding of DRGs and DFRPs in normal physiology, as well as their emerging roles in diseases such as cancer.

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DRG2

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