It takes two to tango: regulation of G proteins by dimerization

Gasper, Raphael; Meyer, Simon De; Gotthardt, Katja; Sirajuddin, Minhajuddin; Wittinghofer, Alfred

doi:10.1038/nrm2689

Cited by 275 publications

(302 citation statements)

References 87 publications

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“…However, the crystal structures of the Toc33 proteins in their monomeric or dimeric form in complex with the GTP analog GMPPNP or GDP (51, 52) did not reveal the expected typical molecular switch thought to be required for G proteins (reviewed in ref. 53). This led to the assumption that a further factor, a so called co-GAP, is required (51).…”

Section: Impact Of the Cytosolic Potra Domain On The Model Of Proteinmentioning

confidence: 99%

Chloroplast Omp85 proteins change orientation during evolution

Sommer

Daum

Groß

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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The majority of outer membrane proteins (OMPs) from Gramnegative bacteria and many of mitochondria and chloroplasts are β-barrels. Insertion and assembly of these proteins are catalyzed by the Omp85 protein family in a seemingly conserved process. All members of this family exhibit a characteristic N-terminal polypeptide-transport-associated (POTRA) and a C-terminal 16-stranded β-barrel domain. In plants, two phylogenetically distinct and essential Omp85's exist in the chloroplast outer membrane, namely Toc75-III and Toc75-V. Whereas Toc75-V, similar to the mitochondrial Sam50, is thought to possess the original bacterial function, its homolog, Toc75-III, evolved to the pore-forming unit of the TOC translocon for preprotein import. In all current models of OMP biogenesis and preprotein translocation, a topology of Omp85 with the POTRA domain in the periplasm or intermembrane space is assumed. Using selfassembly GFP-based in vivo experiments and in situ topology studies by electron cryotomography, we show that the POTRA domains of both Toc75-III and Toc75-V are exposed to the cytoplasm. This unexpected finding explains many experimental observations and requires a reevaluation of current models of OMP biogenesis and TOC complex function.

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Section: Impact Of the Cytosolic Potra Domain On The Model Of Proteinmentioning

confidence: 99%

Chloroplast Omp85 proteins change orientation during evolution

Sommer

Daum

Groß

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…Although they contain G domains that are structurally related to the small G proteins of the Ras superfamily, the corresponding domains in the dynamin superfamily are significantly larger (300 vs. 180 residues) and have a low intrinsic affinity for nucleotide. In addition, GTPases of this family often depend on nucleotide-dependent homodimerization to facilitate GTP hydrolysis rather than heterodimerization with a GTPase activating protein (2). Such a regulatory mechanism has been established for guanylate-binding protein (GBP) and dynamin (3,4).…”

mentioning

confidence: 99%

Structural basis for the nucleotide-dependent dimerization of the large G protein atlastin-1/SPG3A

Byrnes

Sondermann

2011

Proc. Natl. Acad. Sci. U.S.A.

157

260

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The large GTPase atlastin belongs to the dynamin superfamily that has been widely implicated in facilitating membrane tubulation, fission, and in select cases, fusion. Mutations spread across atlastin isoform 1 (atlastin-1) have been identified in patients suffering from hereditary spastic paraplegia (HSP), a neurodegenerative disorder affecting motor neuron function in the lower extremities. On a molecular level, atlastin-1 associates with high membrane curvature and fusion events at the endoplasmic reticulum and cis-Golgi. Here we report crystal structures of atlastin-1 comprising the G and middle domains in two different conformations. Although the orientation of the middle domain relative to the G domain is different in the two structures, both reveal dimeric assemblies with a common, GDP-bound G domain dimer. In contrast, dimer formation in solution is observed only in the presence of GTP and transition state analogs, similar to other G proteins that are activated by nucleotide-dependent dimerization. Analyses of solution scattering data suggest that upon nucleotide binding, the protein adopts a somewhat extended, dimeric conformation that is reminiscent of one of the two crystal structures. These structural studies suggest a model for nucleotide-dependent regulation of atlastin with implications for membrane fusion. This mechanism is affected in several mutants associated with HSP, providing insights into disease pathogenesis.protein structure | neuropathogenic mechanism | tubular membrane network

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“…The three-dimensional structure from pea Toc34 (psToc34) disclosed a homodimeric configuration with bound GDP at the dimerization interface (Sun et al , 2002 ). Such structural arrangement is strikingly reminiscent of a GTPase with its corresponding GAP (Gasper et al , 2009 ). The unifying principle of the TOC receptors is that psToc34 or Arabidopsis Toc33/34 (atToc33/34) dimerizes in a nucleotide-dependent manner and GDP binding moderates the interaction between the G-domains of the respective monomer.…”

Section: The Paradox Of Toc Gtpase Cyclesmentioning

confidence: 99%

“…GTPases typically switch through three common conformational stages: GDP-bound, ' empty ' and GTP-bound states, with the former being the inactive condition. The ' empty ' state (usually) serves as a transient intermediate to replace GDP with GTP in the guanine nucleotide-binding site of the GTPase (Gasper et al , 2009 ). Most often, the switching function of the GTPases is governed by the differing abilities of its conformational states to interact with specific classes of regulator molecules: GTPase-activating proteins (GAPs), which enhance the hydrolytic capacity of GTPases to promote GDP-bound forms; and guanine nucleotide-exchange factors (GEFs), which catalyze the exchange of GDP for GTP in vivo (Aronsson and Jarvis , 2011 ).…”

Section: The Paradox Of Toc Gtpase Cyclesmentioning

confidence: 99%

The gateway to chloroplast: re-defining the function of chloroplast receptor proteins

Chang¹,

Soll²,

Bölter³

2012

Biological Chemistry

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: Chloroplast biogenesis often requires a tight orchestration between gene expression (both plastidial and nuclear) and translocation of ~ 3000 nuclear-encoded proteins into the organelle. Protein translocation is achieved via two multimeric import machineries at the outer (TOC) and inner (TIC) envelope of chloroplast, respectively. Three components constitute the core element of the TOC complex: a β -barrel protein translocation channel Toc75 and two receptor constituents, Toc159 and Toc34. A diverse set of distinct TOC complexes have recently been characterized and these diversified TOC complexes have evolved to coordinate the translocation of differentially expressed proteins. This review aims to describe the recent discoveries relating to the typical characteristics of these distinct TOC complexes, particularly the receptor constituents, which are the main contributors for TOC complex diversification.

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It takes two to tango: regulation of G proteins by dimerization

Cited by 275 publications

References 87 publications

Chloroplast Omp85 proteins change orientation during evolution

Chloroplast Omp85 proteins change orientation during evolution

Structural basis for the nucleotide-dependent dimerization of the large G protein atlastin-1/SPG3A

The gateway to chloroplast: re-defining the function of chloroplast receptor proteins

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