Structure of human guanylate-binding protein 1 representing a unique class of GTP-binding proteins

@article{Prakash2000StructureOH,
  title={Structure of human guanylate-binding protein 1 representing a unique class of GTP-binding proteins},
  author={Balaji Prakash and Gerrit J. K. Praefcke and Louis Renault and Alfred Wittinghofer and Christian Herrmann},
  journal={Nature},
  year={2000},
  volume={403},
  pages={567-571}
}
Interferon-γ is an immunomodulatory substance that induces the expression of many genes to orchestrate a cellular response and establish the antiviral state of the cell. Among the most abundant antiviral proteins induced by interferon-γ are guanylate-binding proteins such as GBP1 and GBP2 (refs 1, 2). These are large GTP-binding proteins of relative molecular mass 67,000 with a high-turnover GTPase activity and an antiviral effect. Here we have determined the crystal structure of full-length… 
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Role of individual domains and identification of internal gap in human guanylate binding protein-1.
How guanylate-binding proteins achieve assembly-stimulated processive cleavage of GTP to GMP
TLDR
It is shown that the isolated amino-terminal G domain of hGBP1 retains the main enzymatic properties of the full-length protein and can cleave GDP directly, and the molecular basis for nucleotide-dependent homodimerization and cleavage of GTP is revealed.
Identification of residues in the human guanylate-binding protein 1 critical for nucleotide binding and cooperative GTP hydrolysis.
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.
Mechanism of GTPase-activity-induced self-assembly of human guanylate binding protein 1.
Dimerization and its role in GMP formation by human guanylate binding proteins.
Biochemical properties of the human guanylate binding protein 5 and a tumor‐specific truncated splice variant
The human guanylate binding protein 5 (hGBP5) belongs to the family of interferon‐γ‐inducible large GTPases, which are well known for their high induction by pro‐inflammatory cytokines. The cellular…
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.
Biochemical and structural characterization of murine GBP7, a guanylate binding protein with an elongated C-terminal tail.
TLDR
It is demonstrated that mGBP7 exhibits a concentration-dependent GTPase activity and an apparent GTP turnover number of 20 min-1 and that this tail has transmembrane characteristics and, interestingly, confocal microscopy analyses reveal that the CT tail is required for recruitment of m GBP7 to the parasitophorous vacuole of Toxoplasma gondii.
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.
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References

SHOWING 1-10 OF 41 REFERENCES
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.
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.
Domains Mediating Intramolecular Folding and Oligomerization of MxA GTPase*
TLDR
MxA sequences located downstream of amino acid 564 were found to strongly interact with an internal domain that includes amino acids 372 to 540, and interaction of two full-length MxA molecules occurred only if at least one of them carried a functional C-terminal leucine zipper motif, suggesting C- terminus back-folding and oligomerization are two alternative outcomes of the same type of interaction.
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TLDR
A model is proposed that suggests that the GTP-binding consensus element located in the NH2-terminal half of MxA is held in an active conformation by strong physical interactions with amino acids from the COOH- terminus.
GTP-bound Human MxA Protein Interacts with the Nucleocapsids of Thogoto Virus (Orthomyxoviridae)*
TLDR
It is proposed that GTP-bound MxA adopts an antivirally active conformation that allows interaction with viral nucleocapsids, thereby impairing their normal function.
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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.
Two families of GTPases dominate the complex cellular response to IFN-gamma.
TLDR
Two small unrelated families of GTPases appear to be dedicated to the IFN-gamma response, since resting levels are negligible and since neither family shows any significant relationship to any other described family of G TPases.
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TLDR
Three different intramolecular binding interactions that may account for the process of dynamin self-assembly are described, suggesting a model in which dynamin molecules first dimerize and are then linked into a chain by a second binding reaction.
Refined crystal structure of the triphosphate conformation of H‐ras p21 at 1.35 A resolution: implications for the mechanism of GTP hydrolysis.
TLDR
A mechanism for GTP hydrolysis involving mainly Gln61 and Glu63 as activating species for in‐line attack of water as well as a mechanism for rate enhancement by GAP is proposed.
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