Ligand-dependent Conformational Plasticity of the Periplasmic Histidine-binding Protein HisJ

Wolf, Amnon; Lee, Kai C.; Kirsch, Jack F.; Ames, Giovanna Ferro‐Luzzi

doi:10.1074/jbc.271.35.21243

Cited by 39 publications

(55 citation statements)

References 63 publications

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“…Accordingly, mutation of these residues may affect K 2 and therefore have opposite effects on the affinities of agonists and antagonists. In agreement with this proposal, amino acids at comparable positions in PBPs such as the histidine-binding protein have been shown to affect the equilibrium constant between the closed and open states (40,41,44). It is interesting to note here that Ser-247 aligns with Ser-73 in LBP and Ser-166 in mGluR1.…”

Section: Selection and Mutagenesis Of Additional Residues Possibly Insupporting

confidence: 66%

Mutagenesis and Modeling of the GABAB Receptor Extracellular Domain Support a Venus Flytrap Mechanism for Ligand Binding

Galvez¹,

Parmentier²,

Joly³

et al. 1999

Journal of Biological Chemistry

197

156

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The ␥-aminobutyric acid type B (GABA B ) receptor is distantly related to the metabotropic glutamate receptor-like family of G-protein-coupled receptors (family 3). Sequence comparison revealed that, like metabotropic glutamate receptors, the extracellular domain of the two GABA B receptor splice variants possesses an identical region homologous to the bacterial periplasmic leucine-binding protein (LBP), but lacks the cysteinerich region common to all other family 3 receptors. A three-dimensional model of the LBP-like domain of the GABA B receptor was constructed based on the known structure of LBP. This model predicts that four of the five cysteine residues found in this GABA B receptor domain are important for its correct folding. This conclusion is supported by analysis of mutations of these Cys residues and a decrease in the thermostability of the binding site after dithiothreitol treatment. Additionally, Ser-246 was found to be critical for CGP64213 binding. Interestingly, this residue aligns with Ser-79 of LBP, which forms a hydrogen bond with the ligand. The mutation of Ser-269 was found to differently affect the affinity of various ligands, indicating that this residue is involved in the selectivity of recognition of GABA B receptor ligands. Finally, the mutation of two residues, Ser-247 and Gln-312, was found to increase the affinity for agonists and to decrease the affinity for antagonists. Such an effect of point mutations can be explained by the Venus flytrap model for receptor activation. This model proposes that the initial step in the activation of the receptor by agonist results from the closure of the two lobes of the binding domain.

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Section: Selection and Mutagenesis Of Additional Residues Possibly Insupporting

confidence: 66%

Mutagenesis and Modeling of the GABAB Receptor Extracellular Domain Support a Venus Flytrap Mechanism for Ligand Binding

Galvez¹,

Parmentier²,

Joly³

et al. 1999

Journal of Biological Chemistry

197

156

View full text Add to dashboard Cite

show abstract

“…For the histidinebinding protein HisJ, the angle of the closed state appears to depend on the ligand and is related to the ability and efficacy of this periplasmic protein to transport the ligand (41). For GluR2, the full VFTM closure is critical for agonist activation and rapid desensitization of the receptor (39,40).…”

Section: Discussionmentioning

confidence: 99%

Closure of the Venus flytrap module of mGlu8 receptor and the activation process: Insights from mutations converting antagonists into agonists

Bessis

Rondard

Gaven

et al. 2002

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

110

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Ca 2؉ , pheromones, sweet taste compounds, and the main neurotransmitters glutamate and ␥-aminobutyric acid activate G proteincoupled receptors (GPCRs) that constitute the GPCR family 3. These receptors are dimers, and each subunit has a large extracellular domain called a Venus flytrap module (VFTM), where agonists bind. This module is connected to a heptahelical domain that activates G proteins. Recently, the structure of the dimer of mGlu1 VFTMs revealed two important conformational changes resulting from glutamate binding. First, agonists can stabilize a closed state of at least one VFTM in the dimer. Second, the relative orientation of the two VFTMs in the dimer is different in the presence of glutamate, such that their C-terminal ends (which are connected to the G protein-activating heptahelical domain) become closer by more than 20 Å. This latter change in orientation has been proposed to play a key role in receptor activation. To elucidate the respective role of VFTM closure and the change in orientation of the VFTMs in family 3 GPCR activation, we analyzed the mechanism of action of the mGlu8 receptor antagonists ACPT-II and MAP4. Molecular modeling studies suggest that these two compounds prevent the closure of the mGlu8 VFTM because of ionic and steric hindrance, respectively. We show here that the replacement of the residues responsible for these hindrances (Asp-309 and Tyr-227, respectively) by Ala allows ACPT-II or MAP4 to fully activate the receptors. These data are consistent with the requirement of the VFTM closure for family 3 GPCR activation.

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“…18) indicating that a large conformational change must take place in the BtuC domains upon BtuFmediated delivery of B12. This delivery process is likely to involve stable binding of BtuF to the transmembrane BtuC subunit based on the results observed with other PBP-dependent bacterial ABC transporters (37). Given the 2-fold symmetry of the BtuC subunits flanking the putative B12-binding site in the transporter, BtuF might be expected to exhibit 2-fold pseudo-symmetry in the regions flanking its B12 binding site.…”

Section: Table 1 E Coli Btuf Refinement Statisticsmentioning

confidence: 99%

Crystal Structures of the BtuF Periplasmic-binding Protein for Vitamin B12 Suggest a Functionally Important Reduction in Protein Mobility upon Ligand Binding

Karpowich¹,

Huang

Smith

et al. 2003

Journal of Biological Chemistry

142

163

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BtuF is the periplasmic binding protein (PBP) for the vitamin B12 transporter BtuCD, a member of the ATPbinding cassette (ABC) transporter superfamily of transmembrane pumps. We have determined crystal structures of Escherichia coli BtuF in the apo state at 3.0 Å resolution and with vitamin B12 bound at 2.0 Å resolution. The structure of BtuF is similar to that of the FhuD and TroA PBPs and is composed of two ␣/␤ domains linked by a rigid ␣-helix. B12 is bound in the "base-on" or vitamin conformation in a wide acidic cleft located between these domains. The C-terminal domain shares structural homology to a B12-binding domain found in a variety of enzymes. The same surface of this domain interacts with opposite surfaces of B12 when comparing ligand-bound structures of BtuF and the homologous enzymes, a change that is probably caused by the obstruction of the face that typically interacts with this domain by the base-on conformation of vitamin B12 bound to BtuF. There is no apparent pseudo-symmetry in the surface properties of the BtuF domains flanking its B12 binding site even though the presumed transport site in the previously reported crystal structure of BtuCD is located in an intersubunit interface with 2-fold symmetry. Unwinding of an ␣-helix in the C-terminal domain of BtuF appears to be part of conformational change involving a general increase in the mobility of this domain in the apo structure compared with the B12-bound structure. As this helix is located on the surface likely to interact with BtuC, unwinding of the helix upon binding to BtuC could play a role in triggering release of B12 into the transport cavity. Furthermore, the high mobility of this domain in free BtuF could provide an entropic driving force for the subsequent release of BtuF required to complete the transport cycle.

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Ligand-dependent Conformational Plasticity of the Periplasmic Histidine-binding Protein HisJ

Cited by 39 publications

References 63 publications

Mutagenesis and Modeling of the GABAB Receptor Extracellular Domain Support a Venus Flytrap Mechanism for Ligand Binding

Mutagenesis and Modeling of the GABAB Receptor Extracellular Domain Support a Venus Flytrap Mechanism for Ligand Binding

Closure of the Venus flytrap module of mGlu8 receptor and the activation process: Insights from mutations converting antagonists into agonists

Crystal Structures of the BtuF Periplasmic-binding Protein for Vitamin B12 Suggest a Functionally Important Reduction in Protein Mobility upon Ligand Binding

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