Abstract
The CAP protein superfamily (Cysteine-rich secretory proteins (CRISPs), Antigen 5 (Ag5), and Pathogenesis-related 1 (PR-1) proteins) is widely distributed, but for toxinologists, snake venom CRISPs are the most familiar members. Although CRISPs are found in the majority of venoms, very few of these proteins have been functionally characterized, but those that have been exhibit diverse activities. Snake venom CRISPs (svCRISPs) inhibit ion channels and the growth of new blood vessels (angiogenesis). They also increase vascular permeability and promote inflammatory responses (leukocyte and neutrophil infiltration). Interestingly, CRISPs in lamprey buccal gland secretions also manifest some of these activities, suggesting an evolutionarily conserved function. As we strive to better understand the functions that CRISPs serve in venoms, it is worth considering the broad range of CRISP physiological activities throughout the animal kingdom. In this review, we summarize those activities, known crystal structures and sequence alignments, and we discuss predicted functional sites. CRISPs may not be lethal or major components of venoms, but given their almost ubiquitous occurrence in venoms and the accelerated evolution of svCRISP genes, these venom proteins are likely to have functions worth investigating.
Highlights
The CAP protein superfamily (Cysteine-rich secretory proteins (CRISPs), Antigen 5 (Ag5), and Pathogenesis-related 1 (PR-1) proteins), occasionally called the sperm coating protein (SCP) orTpx-1/Ag5/PR-1/Sc7 (TAPS) family, occurs in a wide range of organisms
We hypothesize that formation of a parallel β-sheet between the Small serum protein-2 (SSP-2) β5 strand and the triflin β4 strand may allow the SSP-2 β1 strand to fit into the cavity between the CAP/PR-1 and Cysteine-Rich Domain (CRD)/ICR domains of triflin, thereby blocking the Zn2+ binding site and stabilizing the interaction
These findings indicate that our model provides significant structural insight into the human PSP94–Cysteine-Rich Secretory Proteins (CRISPs)-3 complex, which has been debated for many years
Summary
The CAP protein superfamily (Cysteine-rich secretory proteins (CRISPs), Antigen 5 (Ag5), and Pathogenesis-related 1 (PR-1) proteins), occasionally called the sperm coating protein (SCP) or. Toxins 2020, 12, 175 comprises approximately 150–160 amino acids and includes four signature sequences, as defined in the PROSITE Database (http://www.expasy.ch/prosite/): CAP1, [GDER][HR][FYWH][TVS][QA][LIVM][LIVMA]Wxx[STN]; CAP2, [LIVMFYH][LIVMFY]xC[NQRHS]Yx[PARH]x[GL]N[LIVMFYWDN]; CAP3 (HNxxR); and CAP4 (G[EQ]N[ILV]) Most proteins in this superfamily have only one CAP/PR-1 domain; a few species of parasitic helminths have proteins with more than one [1]. Mammalian CRISPs are associated with reproduction, cancer, and immune responses [28,29] In addition to these activities, CRISPs have been identified as toxins in venom glands of snakes, lizards, spiders, scorpions, and cone snails [30,31,32,33,34]. Target binding to alter cellular signaling cascades is a common function of CRISPs and other proteins of the CAP superfamily. For structure descriptions we have used residue numbering from triflin and natrin, well-characterized svCRISPs with published structures (Figure 1)
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