Structural Analysis of the Human Golgi-associated Plant Pathogenesis Related Protein GAPR-1 Implicates Dimerization as a Regulatory Mechanism

Serrano, Ramón; Kuhn, Audrey; Hendricks, Astrid; Helms, J. Bernd; Sinning, Irmgard; Groves, Matthew R.

doi:10.1016/j.jmb.2004.03.015

Cited by 68 publications

(84 citation statements)

References 47 publications

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“…The tight packing of the α-helices on both sides of the central β-sheet results in a compact, bipartite molecular core, which is stabilized by hydrophobic interactions, multiple hydrogen bonds, and two highly conserved disulfide bonds ( Figure 1B). These features are thought to provide the high thermal, pH, and proteolytic stability reported for CAP proteins, consistent with the structural requirements of an extracellular function (11)(12)(13)(14).…”

Section: Structure Of Cap Proteinssupporting

confidence: 56%

“…Modeling of the Tex31 sequence to the structure of PR-1 and Ag5 was consistent with a possible catalytic role of the conserved surfaceexposed histidine and glutamic acid residues (15). 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).…”

Section: Proposed Functions Of Cap Proteinsmentioning

confidence: 75%

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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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Section: Structure Of Cap Proteinssupporting

confidence: 56%

Section: Proposed Functions Of Cap Proteinsmentioning

confidence: 75%

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

Schneiter

Pietro

2013

BioMolecular Concepts

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“…1), which form a globular domain that includes an --sandwich core and has a fold similar to the pathogenesis-related proteins of group 1 (PR-1) proteins, e.g. P14a (Fernandez et al, 1997) and GAPR1 (Serrano et al, 2004), and the antigen 5 proteins, e.g. Ves v 5 (Henriksen et al, 2001).…”

Section: Overall Structures Of Pstx and Pdc And Comparison With Othermentioning

confidence: 99%

Structures of pseudechetoxin and pseudecin, two snake-venom cysteine-rich secretory proteins that target cyclic nucleotide-gated ion channels: implications for movement of the C-terminal cysteine-rich domain

Suzuki

Yamazaki

Brown

et al. 2008

Acta Crystallogr D Biol Crystallogr

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Cyclic nucleotide-gated (CNG) ion channels play pivotal roles in sensory transduction by retinal photoreceptors and olfactory neurons. The elapid snake toxins pseudechetoxin (PsTx) and pseudecin (Pdc) are the only known protein blockers of CNG channels. These toxins belong to a cysteinerich secretory protein (CRISP) family containing an N-terminal pathogenesis-related proteins of group 1 (PR-1) domain and a C-terminal cysteine-rich domain (CRD). PsTx and Pdc are highly homologous proteins, but their blocking affinities on CNG channels are different: PsTx blocks both the olfactory and retinal channels with $15-30-fold higher affinity than Pdc. To gain further insights into their structure and function, the crystal structures of PsTx, Pdc and Zn 2+-bound Pdc were determined. The structures revealed that most of the amino-acid-residue differences between PsTx and Pdc are located around the concave surface formed between the PR-1 domain and the CRD, suggesting that the concave surface is functionally important for CNG-channel binding and inhibition. A structural comparison in the presence and absence of Zn 2+ ion demonstrated that the concave surface can open and close owing to movement of the CRD upon Zn 2+ binding. The data suggest that PsTx and Pdc occlude the pore entrance and that the dynamic motion of the concave surface facilitates interaction with the CNG channels.

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“…Firstly, glioma pathogenesis-related 2 protein (GLIPR-2/RTVP-1/GAPR-1) is the smallest of the mammalian CAPs and the one most closely related to yeast Pry1 (3,4). It is remarkable as it is thus far the only CAP protein that is not secreted (5). Instead, the protein is myristoylated and associates with the cytosolic surface of the Golgi membrane (6).…”

mentioning

confidence: 99%