Cobra CRISP Functions as an Inflammatory Modulator via a Novel Zn2+- and Heparan Sulfate-dependent Transcriptional Regulation of Endothelial Cell Adhesion Molecules

Wang, Yuling; Kuo, Je-Hung; Lee, Shao Chen; Liu, Jai Shin; Hsieh, Yin-Cheng; Shih, Yu Tsung; Chen, Chun‐Jung; Chiu, Jeng Jiann; Wu, Wenwen

doi:10.1074/jbc.m110.146290

Cited by 81 publications

(92 citation statements)

References 59 publications

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“…These surface residues were suggested to adopt a conformation similar to the active site histidyl and glutamyl residues of several Zn-dependent proteases and were suggested to form part of a putative active site triad of a CAP protein with a reported in vitro protease activity, Tex31 ( 5,6 ). Apart from a possible catalytic activity of CAP family members, the CAP domain has been suggested to form a stable scaffold for biological interactions with other proteins ( 7 ).…”

Section: ( 3 )mentioning

confidence: 99%

“…For example, CAP proteins harboring a C-terminal cysteine-rich domain, the defi ning feature of the CRISP subfamily, have been associated with modulation of the activity of ion channels, which might account for their role in sperm maturation and venom toxicity ( 6,8,9 ). However, whether the cysteine-rich domain of CRISP proteins acts directly on the ion channel or whether these proteins affect the channel's activity more indirectly, for example through modulation of the lipid composition of the plasma membrane, remains to be established.…”

Section: ( 3 )mentioning

confidence: 99%

See 1 more Smart Citation

The caveolin-binding motif of the pathogen-related yeast protein Pry1, a member of the CAP protein superfamily, is required for in vivo export of cholesteryl acetate

Choudhary

Darwiche

Gfeller

et al. 2014

Journal of Lipid Research

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including immune defense in mammals and plants, pathogen virulence, sperm maturation and fertilization, venom toxicity, and prostate and brain cancer. Named after the founding members of this protein superfamily (cysteine-rich secretory protein, antigen 5, and pathogenesis-related 1), the CAP superfamily comprises more than 4,500 members in over 1,500 species, and family members are present in all kingdoms of life. Almost all CAP proteins are secreted glycoproteins and they are stable in the extracellular space over a wide range of conditions. All members of this superfamily share a common CAP domain of approximately 150 amino acids, which adopts a unique ␣ -␤ -␣ sandwich fold. The structural conservation of this domain suggests that CAP proteins exert a fundamentally similar function. The molecular mode of action of the CAP proteins, however, has remained enigmatic [for reviews see ( 1, 2 )].CAP proteins share limited sequence identity with each other and are characterized by two PROSITE-recognized sequence motifs, referred to as the CRISP family signature (shaded boxes in Fig. 1 ). An early comparison of the structure of the plant pathogenesis-related protein (PR)-1 with that of the human glioma pathogenesis-related protein 1 (GLIPR1) revealed that the small and structurally conserved 17-21 kDa CAP domain adopts a unique ␣ -␤ -␣ sandwich fold, in which a three-stranded anti-parallel ␤ -sheet is fl anked by three helices on one side, and a fourth helix on the other ( 3 ). This three-stacked layer is stabilized by hydrophobic interactions, multiple hydrogen bonds, and by two highly conserved disulfi de bonds. These features are thought to provide the thermal, pH, and proteolytic stability required for the extracellular function of these proteins ( 3, 4 ). The CAP domain harbors four highly 28 February 2014. Published, JLR Papers in Press, March 5, 2014 DOI 10.1194 The caveolin-binding motif of the pathogen-related yeast protein Pry1, a member of the CAP protein superfamily, is required for in vivo export of cholesteryl acetate Abbreviations: DOPE, discrete optimized protein energy; GLIPR1, glioma pathogenesis-related protein 1; PR, pathogenesis-related protein; OD, optical density; PDB, protein data base; Pry, pathogen-related yeast; RMSD, root mean square deviation; SC, synthetic complete. Manuscript received 15 January 2014 and in revised form

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Section: ( 3 )mentioning

confidence: 99%

Section: ( 3 )mentioning

confidence: 99%

The caveolin-binding motif of the pathogen-related yeast protein Pry1, a member of the CAP protein superfamily, is required for in vivo export of cholesteryl acetate

Choudhary

Darwiche

Gfeller

et al. 2014

Journal of Lipid Research

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“…The vast majority of reported CAP structures are of snake-venom CRISPs, including PDB entries 2dda, 2ddr, 1xx5, 1xta, 3mz8, 1wvr and 1rc9 (Suzuki et al, 2008;Wang et al, 2005Wang et al, , 2010Shikamoto et al, 2005;Guo et al, 2005). Two reported CAP structures, PDB entries 1u53 and 1nt8, are of Ancylosoma-secreted proteins from hookworms (Asojo et al, 2005;Asojo, 2011).…”

Section: Introductionmentioning

confidence: 99%

Structural studies of human glioma pathogenesis-related protein 1

Asojo

Koski²,

Bonafé³

2011

Acta Crystallogr D Biol Cryst

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Human glioma pathogenesis-related protein 1 (GLIPR1) is a membrane protein that is highly upregulated in brain cancers but is barely detectable in normal brain tissue. GLIPR1 is composed of a signal peptide that directs its secretion, a conserved cysteine-rich CAP (cysteine-rich secretory proteins, antigen 5 and pathogenesis-related 1 proteins) domain and a transmembrane domain. GLIPR1 is currently being investigated as a candidate for prostate cancer gene therapy and for glioblastoma targeted therapy. Crystal structures of a truncated soluble domain of the human GLIPR1 protein (sGLIPR1) solved by molecular replacement using a truncated polyalanine search model of the CAP domain of stecrisp, a snake-venom cysteine-rich secretory protein (CRISP), are presented. The correct molecular-replacement solution could only be obtained by removing all loops from the search model. The native structure was refined to 1.85 Å resolution and that of a Zn 2+ complex was refined to 2.2 Å resolution. The latter structure revealed that the putative binding cavity coordinates Zn 2+ similarly to snake-venom CRISPs, which are involved in Zn 2+ -dependent mechanisms of inflammatory modulation. Both sGLIPR1 structures have extensive flexible loop/turn regions and unique charge distributions that were not observed in any of the previously reported CAP protein structures. A model is also proposed for the structure of full-length membrane-bound GLIPR1.

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“…The lack of a conserved serine in this putative active-site triad led others to propose that dimerization of CAP proteins is required to complete the formation of the active site (14). However, subsequent studies failed to detect protease activity with purified CAP family members, and a conclusive demonstration of the protease activity for a mammalian, fungal, or plant CAP protein is still lacking (11,16,17). Apart from a possible catalytic activity, the CAP domain has been suggested to form a stable scaffold for biological interactions with other proteins (18), although no interactions of plant PR-1 with other proteins have been detected (19).…”

Section: Proposed Functions Of Cap Proteinsmentioning

confidence: 99%

The CAP protein superfamily: function in sterol export and fungal virulence

Schneiter

Pietro

2013

BioMolecular Concepts

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CAP superfamily proteins, also known as spermcoating proteins, are found in all kingdoms of life and have been implicated in a variety of physiological contexts, including immune defense in plants and mammals, sperm maturation and fertilization, fungal virulence, and toxicity of insect and reptile venoms as well as prostate and brain cancer. CAP family members are mostly secreted glycoproteins that are highly stable in the extracellular fluid. All members of the superfamily share a common CAP domain of approximately 150 amino acids, which adopts a unique α-β-α sandwich fold. The conserved structure suggests that CAP proteins exert fundamentally similar functions. However, the molecular mode of action of this protein family has remained enigmatic. The budding yeast Saccharomyces cerevisiae has three CAP family members designated Pry (pathogen related in yeast), and recent evidence indicates that they act as sterol-binding and export proteins. Expression of the mammalian CAP protein CRISP2, which binds sterols in vitro, complements the sterol export defect of a yeast pry mutant, suggesting that sterol binding and export is conserved among different CAP family members. Collectively, these observations suggest that CAP family members constitute a novel class of secreted extracellular sterol-binding proteins. A ligand-binding activity of the CAP domain could explain many of the biological activities attributed to these proteins. For example, the strong induction of plant pathogenesis-related 1 protein upon exposure to pathogens may serve to inhibit pathogen proliferation by extracting sterols from the pathogen membrane. Similarly, the presence of these proteins in the venom of toxic insects and reptiles or in the secretome of pathogenic fungi might inflict damage by sequestering sterols or related small hydrophobic compounds from the host tissue.

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Cobra CRISP Functions as an Inflammatory Modulator via a Novel Zn2+- and Heparan Sulfate-dependent Transcriptional Regulation of Endothelial Cell Adhesion Molecules

Cited by 81 publications

References 59 publications

The caveolin-binding motif of the pathogen-related yeast protein Pry1, a member of the CAP protein superfamily, is required for in vivo export of cholesteryl acetate

The caveolin-binding motif of the pathogen-related yeast protein Pry1, a member of the CAP protein superfamily, is required for in vivo export of cholesteryl acetate

Structural studies of human glioma pathogenesis-related protein 1

The CAP protein superfamily: function in sterol export and fungal virulence

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