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… 
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.
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.
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.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 32 REFERENCES
Structure of human guanylate-binding protein 1 representing a unique class of GTP-binding proteins
TLDR
From the structure and biochemical experiments reported here, GBP1 appears to belong to the group of large GTP-binding proteins that includes Mx and dynamin, the common property of which is the ability to undergo oligomerization with a high concentration-dependent GTPase activity.
Interferon-induced guanylate-binding proteins lack an N(T)KXD consensus motif and bind GMP in addition to GDP and GTP.
TLDR
The primary structures of interferon (IFN)-induced guanylate-binding proteins (GBPs) were deduced from cloned human and murine cDNAs and it is demonstrated that human and Murine cells contain at least two genes encoding IFN-induced GBPs.
Triphosphate structure of guanylate‐binding protein 1 and implications for nucleotide binding and GTPase mechanism
TLDR
The structure of human GBP1 in complex with the non‐hydrolysable GTP analogue GppNHp is presented, which has consequences for the GTPase mechanism of hGBP1 and possibly of other large GTP‐binding proteins.
Nucleotide-binding characteristics of human guanylate-binding protein 1 (hGBP1) and identification of the third GTP-binding motif.
TLDR
The third canonical GTP-binding motif was identified and verified its role in nucleotide recognition by mutational analysis and will serve as a basis for the determination of the differential biological functions of the three nucleotide states and for the elucidation of the unique mechanism of nucleotide hydrolysis catalysed by hGBP1.
The interferon-induced 67-kDa guanylate-binding protein (hGBP1) is a GTPase that converts GTP to GMP.
TLDR
In vitro modification assays with radiolabeled mevalonic acid and farnesyl pyrophosphate showed that the CaaX motif at the C terminus of hGBP1 functions as an isoprenylation signal, indicating that h GBP1 is a GTPase with novel biochemical properties that may be membrane-associated in eukaryotic cells.
IIGP1, an Interferon-γ-inducible 47-kDa GTPase of the Mouse, Showing Cooperative Enzymatic Activity and GTP-dependent Multimerization*
TLDR
This study clearly adds IIGP1 and thus the p47 GTPases to the small group of cooperative GTPase families that appear to characterize the development of intracellular resistance during the interferon response to infection.
Golgi targeting of human guanylate-binding protein-1 requires nucleotide binding, isoprenylation, and an IFN-gamma-inducible cofactor.
TLDR
Evidence is presented that hGBP-1 can associate with the Golgi apparatus and two nonhydrolyzing mutants of hGBp-1, corresponding to active mutants of Ras family proteins, failed to constitutively associate withThe Golgi.
...
1
2
3
4
...