How guanylate-binding proteins achieve assembly-stimulated processive cleavage of GTP to GMP

@article{Ghosh2006HowGP,
  title={How guanylate-binding proteins achieve assembly-stimulated processive cleavage of GTP to GMP},
  author={Agnidipta Ghosh and Gerrit J. K. Praefcke and Louis Renault and Alfred Wittinghofer and Christian Herrmann},
  journal={Nature},
  year={2006},
  volume={440},
  pages={101-104}
}
Interferons are immunomodulatory cytokines that mediate anti-pathogenic and anti-proliferative effects in cells. Interferon-γ-inducible human guanylate binding protein 1 (hGBP1) belongs to the family of dynamin-related large GTP-binding proteins, which share biochemical properties not found in other families of GTP-binding proteins such as nucleotide-dependent oligomerization and fast cooperative GTPase activity. hGBP1 has an additional property by which it hydrolyses GTP to GMP in two… 
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Structural basis for GTP-induced dimerization and antiviral function of guanylate-binding proteins
TLDR
The results point to a GTP-induced dimerization mode that is likely conserved among all GBP members and provide insights into the molecular determinants of their antiviral function.
Insight into Temperature Dependence of GTPase Activity in Human Guanylate Binding Protein-1
TLDR
This study provides the first thermodynamic insight into the effect of temperature in the product formation of hGBP1 and indicates that GDP formation occurs through the reversible dissociation of GDP-bound enzyme dimer to monomer, which further reversibly dissociates to give the product.
Dimerization and its role in GMP formation by human guanylate binding proteins.
Transient Kinetic Investigation of GTP Hydrolysis Catalyzed by Interferon-γ-induced hGBP1 (Human Guanylate Binding Protein 1)*
TLDR
It is suggested that slow dissociation of the GMP-bound homodimer gives rise to the burst behavior and controls the steady state activity in GTP hydrolysis of human guanylate binding protein 1.
Mechanism of GTPase-activity-induced self-assembly of human guanylate binding protein 1.
Role of individual domains and identification of internal gap in human guanylate binding protein-1.
Tetrameric assembly of hGBP1 is crucial for both stimulated GMP formation and antiviral activity.
TLDR
The present study highlights the importance of hGBP1 tetramer in stimulated GMP formation, but also demonstrates its role in the antiviral activity against hepatitis C virus.
Nucleotide-dependent farnesyl switch orchestrates polymerization and membrane binding of human guanylate-binding protein 1
TLDR
It is discovered that binding of a substrate molecule, GTP, to the enzyme triggers the release of an aforemasked lipid anchor, which results in GBP polymerization on the one hand and in the attachment of GBPs to lipid membranes on the other, which leads to the membrane tethering.
The guanine cap of human guanylate‐binding protein 1 is responsible for dimerization and self‐activation of GTP hydrolysis
TLDR
The guanine cap of hGBP1 is the key structural element responsible for dimerization, and is thereby essential for self‐activation of the GTPase activity, and an intramolecular polar contact is identified whose mutation leads to a loss of self‐ activation capability and controlled oligomer formation.
The alpha helix of the intermediate region in hGBP-1 acts as a coupler for enhanced GMP formation.
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References

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TLDR
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TLDR
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TLDR
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TLDR
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