The binding protein of corticotropin-releasing factor: Ligand-binding site and subunit structure

Jahn, Olaf; Eckart, Klaus; Brauns, Olaf; Tezval, Hossein; Spiess, Joachim

doi:10.1073/pnas.192449299

Cited by 49 publications

(49 citation statements)

References 36 publications

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“…It is possible that there may be dynamic interplay between the two receptor subtypes in NAcc during pair bonding behavior, and it might be interesting to further explore the cellular phenotypes of CRF 1 -and CRF 2 -expressing neurons, or to see if CRF 1 and CRF 2 receptors might even colocalize to the same neurons. It is also possible that other agents such as the CRF binding protein, which may act as a reservoir for endogenous CRF, may be involved (Jahn, Eckart, Brauns, Tezval, and Spiess, 2002).…”

Section: Discussionmentioning

confidence: 99%

CRF receptors in the nucleus accumbens modulate partner preference in prairie voles

Lim

Liu

Ryabinin

et al. 2007

Hormones and Behavior

102

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Recent evidence suggests a role for corticotropin-releasing factor (CRF) in the regulation of pair bonding in prairie voles. We have previously shown that monogamous and non-monogamous vole species have dramatically different distributions of CRF receptor type 1 (CRF 1 ) and CRF receptor type 2 (CRF 2 ) in the brain, and that CRF 1 and CRF 2 receptor densities in the nucleus accumbens (NAcc) are correlated with social organization. Monogamous prairie and pine voles have significantly lower levels of CRF receptor type 1 (CRF 1 ), and significantly higher levels of type 2 (CRF 2 ) binding, in NAcc than non-monogamous meadow and montane voles. Here, we report that microinjections of CRF directly into the NAcc accelerate partner preference formation in male prairie voles. Control injections of CSF into NAcc, and CRF into caudate-putamen, did not facilitate partner preference. Likewise, CRF injections into NAcc of non-monogamous meadow voles also did not facilitate partner preference. In prairie voles, this CRF-facilitation effect was blocked by co-injection of either CRF 1 or CRF 2 receptor antagonists into NAcc. Immunocytochemical staining for CRF and Urocortin-1 (Ucn-1), two endogenous ligands for CRF 1 or CRF 2 receptors in the brain, revealed that CRF, but not Ucn-1, immunoreactive fibers were present in NAcc. This supports the hypothesis that local CRF release into NAcc could activate CRF 1 or CRF 2 receptors in the region. Taken together, our results reveal a novel role for accumbal CRF systems in social behavior.Keywords nucleus accumbens; attachment; CRF1; CRF2; corticotropin-releasing factor; corticotrophinreleasing hormone; vole; neuropeptide receptors; pair bond; social behavior; monogamy; species differencesThe corticotropin-releasing factor (CRF) system is involved in the neurobiology underlying stress and anxiety, but much less is known about its role in social behavior. Microtine rodents exhibit diverse social organizations and thus offer an excellent comparative approach in the study of the neurobiology of social behavior (Young and Wang, 2004 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. (Getz, Carter, and Gavish, 1981;Salo, Shapiro, and Dewsbury, 1993). In contrast, closely-related meadow (Microtus pennsylvanicus) and montane voles (Microtus montanus) are promiscuous and solitary (Gruder-Adams and Getz, 1985;Shapiro and Dewsbury, 1990). Past research has revealed that the brain distribution of neuropeptide receptors for oxytocin and vasopressin appears to be responsible for the species differences in social organization (Insel and Shapiro, 1992;In...

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Section: Discussionmentioning

confidence: 99%

CRF receptors in the nucleus accumbens modulate partner preference in prairie voles

Lim

Liu

Ryabinin

et al. 2007

Hormones and Behavior

102

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“…Because CRF-BP has no known paralogous genes, we cannot derive structural information from similar folds in related proteins. On the basis of photoaffinity labeling experiments with r/hCRF-(6 -33), a pair of arginines in CRF-BP, Arg 46 and Arg 59 , was identified as part of the ligand binding site of rat CRF-BP for CRF (26). The binding interface of CRF-BP was proposed to consist of a linear conformation of a stretch of N-terminal amino acids in CRF-BP that interacts with the ␣-helical CRF peptide in antiparallel fashion: Arg 46 interacting with the C terminus and Arg 59 with the N terminus of the peptide (26).…”

Section: Corticotropin Releasing Factor (Crf)mentioning

confidence: 99%

Residues of Corticotropin Releasing Factor-binding Protein (CRF-BP) That Selectively Abrogate Binding to CRF but Not to Urocortin 1

Huising

Vaughan

Shah

et al. 2008

Journal of Biological Chemistry

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Corticotropin releasing factor-binding protein (CRF-BP) binds CRF and urocortin 1 (Ucn 1) with high affinity, thus preventing CRF receptor (CRFR) activation. Despite recent progress on the molecular details that govern interactions between CRF family neuropeptides and their cognate receptors, little is known concerning the mechanisms that allow CRF-BP to bind CRF and Ucn 1 with picomolar affinity. We conducted a comprehensive alanine scan of 76 evolutionarily conserved residues of CRF-BP and identified several residues that differentially affected the affinity for CRF over Ucn 1. We determined that both neuropeptides derive their similarly high affinity from distinct binding surfaces on CRF-BP. Alanine substitutions of arginine 56 (R56A) and aspartic acid 62 (D62A) reduce the affinity for CRF by ϳ100-fold, while only marginally affecting the affinity for Ucn 1.

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“…Then the mixture was irradiated with UV-light (400 watt metal vapor lamp, Ultratech, Osram, Germany) on ice for 30 min. To avoid photodamage of the protein UV light with wavelengths below 300 nm was filtered out by a special glass filter plate (B270, Schott, Germany) (21,22). The photoadducts were analyzed by Western blotting using anti-RGS-His 6 or anti-biotin monoclonal antibodies as primary antibodies and a horseradish peroxidaseconjugated goat anti-mouse antibody as secondary antibody.…”

Section: Construction Of Expressionmentioning

confidence: 99%

“…Competition experiments indicated that the two Bpa 66 peptides acted as effective inhibitors of P23-modification, whereas the two Bpa 62 and the two Bpa 77 peptides had only a low inhibitory activity (not shown). For photocrosslinking, 1 M FGE-His was incubated on ice with a 50-fold molar excess of the respective Bpa peptide and UV-illuminated for 30 min under conditions avoiding photodamage of the protein (22). Western blot analysis using anti-biotin antibodies demonstrated that the cysteine and alanine form of the Bpa 77 peptide was covalently cross-linked to FGE (Fig.…”

Section: Table I Fge-mediated Turnover Of Peptides Derived From Humanmentioning

confidence: 99%

Molecular Characterization of the Human Cα-formylglycine-generating Enzyme

Preusser-Kunze¹,

Mariappan²,

Schmidt³

et al. 2005

Journal of Biological Chemistry

139

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C␣-formylglycine (FGly) is the catalytic residue in the active site of sulfatases. In eukaryotes, it is generated in the endoplasmic reticulum by post-translational modification of a conserved cysteine residue. The FGly-generating enzyme (FGE), performing this modification, is an endoplasmic reticulum-resident enzyme that upon overexpression is secreted. Recombinant FGE was purified from cells and secretions to homogeneity. Intracellular FGE contains a high mannose type N-glycan, which is processed to the complex type in secreted FGE. Secreted FGE shows partial N-terminal trimming up to residue 73 without loosing catalytic activity. FGE is a calciumbinding protein containing an N-terminal (residues 86 -168) and a C-terminal (residues 178 -374) protease-resistant domain. The latter is stabilized by three disulfide bridges arranged in a clamp-like manner, which links the third to the eighth, the fourth to the seventh, and the fifth to the sixth cysteine residue. The innermost cysteine pair is partially reduced. The first two cysteine residues are located in the sequence preceding the Nterminal protease-resistant domain. They can form intramolecular or intermolecular disulfide bonds, the latter stabilizing homodimers. The C-terminal domain comprises the substrate binding site, as evidenced by yeast two-hybrid interaction assays and photocrosslinking of a substrate peptide to proline 182. Peptides derived from all known human sulfatases served as substrates for purified FGE indicating that FGE is sufficient to modify all sulfatases of the same species.

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The binding protein of corticotropin-releasing factor: Ligand-binding site and subunit structure

Cited by 49 publications

References 36 publications

CRF receptors in the nucleus accumbens modulate partner preference in prairie voles

CRF receptors in the nucleus accumbens modulate partner preference in prairie voles

Residues of Corticotropin Releasing Factor-binding Protein (CRF-BP) That Selectively Abrogate Binding to CRF but Not to Urocortin 1

Molecular Characterization of the Human Cα-formylglycine-generating Enzyme

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