326
9 Toxic Proteins and Peptides
in the mouse, is the a-type toxin Aa-II of the
North African species Androctonus australis.
Most insect-specific toxins differ characteristically
from the mammal-specific toxins in their amino
acid sequences, spatial structures and modes of
action [18]; some insect toxins, however, are quite
similar to the mammal-specific ones [14, 40].
Amongst the insect-specific toxins, one type
blocks action potentials and thus produces a flaccid paralysis, and the other type induces repetitive firing of the motor nerves and therefore produces a spastic paralysis [14].
The approximately 25000 spider species all
possess poison glands on their mouth appendages
(chelicera) and these glands serve in the catching
of prey. The crude poison of the spiders also contains numerous components, including biogenic
amines, polyamines, enzymes and toxic proteins
[5, 20, 54, 62]. Only a few species are dangerous
for humans, the most dangerous being Atrax
robustus, which is found only in metropolitan
Sydney and has led to 13 deaths in the last 60
years. The venom of the funnel-web spider Agelenopsis aperta contains both postsynaptic-acting
acylpolyamines (a-agatoxins) and two classes of
peptides which presynaptically affect the glutamatergic neuromuscular junction of insects. Of
these latter, the Il-agatoxins (36-38 amino acids)
have an activating effect, whilst the w-agatoxins
(::5 66 amino acids) are inhibitory [1]. Further
toxic peptides, with 36-77 amino acids, from
other spider species have been sequenced [10, 29,
54, 64]; their phylogenetic relationships to each
other are not yet known.
9.3.2 Insect Venoms
Next to those of the scorpions, the bestinvestigated arthropod venoms are those of the
honeybee Apis melli/era and several wasp species.
Like all poisonous secretions examined in any
detail, the venoms of the Hymenoptera are found
to be complex mixtures of substances. Amongst
the low molecular weight compounds are biogenic amines (histamine, 5-hydroxytryptamine,
dopamine, adrenalin, noradrenalin, acetylcholine), phospholipids, sugars and free amino acids
[5, 55]. Electrophoresis distinguishes 25-40
polypeptides in the toxic secretions of different
Hymenoptera. Various enzymes are found
amongst the proteins. The phospholipase A2
which makes up 12 % of the dry weight of bee
venom is a basic polypeptide of 129 amino acids
of known sequence. Wasp venoms also contain phospholipases of the types Al and B [33,
55]. The hyaluronidase of bee and other hymenopteran venoms promotes the spread of the
toxic substances in the tissues [32, 55]. The
hymenoptera-venoms also include esterases, glycosidases and protease inhibitors [55]. Enzyme
proteins constitute approximately 13-15 % of the
dry weight of worker bee venom, whereas that of
the queen bee contains only traces of phospholipase and hyaluronidase.
The most investigated components of
hymenoptera-venoms are the bioactive peptides,
which, for example, constitute 50-60 % of the
dry weight of bee venom. On the basis of their
pharmacological effects, one can distinguish
above all haemolytic, neurotoxic and kinin-like
peptides; these are distributed quite irregularly
amongst the different hymenopteran groups. The
haemolytic melittin (Fig.9.4a) predominates in
bee venom; in contrast, there are no haemolytic
proteins in wasp venom but various kinins are
found, which are lacking in the bee (Fig. 9.3).
Melittin is a peptide of 26 amino acids with an
amidated C-terminus and an N-terminus which is
formylated in about 10% of the molecules. On
the extended molecule, a non-polar N-terminal
section of 20 amino acids and a very basic Cterminal section can be differentiated (Fig. 9.4a).
This structure relates to the unusually strong
interaction with lipid double membranes: melittin
has a haemolytic effect and reduces the surface
tension of water to a much greater extent than do
all other peptides. Solutions of low ionic strength
contain the monomer, whereas in higher ionic
strength solutions and in the poison reservoir the
venom is found as a tetramer with the form of a
double cross [67]. Species related to the honey
bee have somewhat modified sequences
(Fig. 9.4a). The sequence of prepro-melittin has
been determined by the analysis of mRNA from
honey-bee venom glands: it consists of 70 amino
acids, of which 1-21 form the signal sequence and
22-43 form the pro-sequence. Mature melittin
consists of amino acids 44-70, with the terminal
glycine taking part in the amidation of the Cterminus [73]. The most important neurotoxic
component of bee venom is apamin, a basic peptide of only 18 amino acids (Fig.9.4a). Melittin
itself has a weak degranulating and histaminereleasing activity on mammalian mast cells; a
much higher activity is shown by the mast-cell
degranulating peptide (MCD) , an extremely
basic peptide (pI = 12) with 22 amino acids, of
which none is acidic and no fewer than 7 are basic
(Fig.9.4a). Finally, bee venom contains small
9 Toxic Proteins and Peptides
in the mouse, is the a-type toxin Aa-II of the
North African species Androctonus australis.
Most insect-specific toxins differ characteristically
from the mammal-specific toxins in their amino
acid sequences, spatial structures and modes of
action [18]; some insect toxins, however, are quite
similar to the mammal-specific ones [14, 40].
Amongst the insect-specific toxins, one type
blocks action potentials and thus produces a flaccid paralysis, and the other type induces repetitive firing of the motor nerves and therefore produces a spastic paralysis [14].
The approximately 25000 spider species all
possess poison glands on their mouth appendages
(chelicera) and these glands serve in the catching
of prey. The crude poison of the spiders also contains numerous components, including biogenic
amines, polyamines, enzymes and toxic proteins
[5, 20, 54, 62]. Only a few species are dangerous
for humans, the most dangerous being Atrax
robustus, which is found only in metropolitan
Sydney and has led to 13 deaths in the last 60
years. The venom of the funnel-web spider Agelenopsis aperta contains both postsynaptic-acting
acylpolyamines (a-agatoxins) and two classes of
peptides which presynaptically affect the glutamatergic neuromuscular junction of insects. Of
these latter, the Il-agatoxins (36-38 amino acids)
have an activating effect, whilst the w-agatoxins
(::5 66 amino acids) are inhibitory [1]. Further
toxic peptides, with 36-77 amino acids, from
other spider species have been sequenced [10, 29,
54, 64]; their phylogenetic relationships to each
other are not yet known.
9.3.2 Insect Venoms
Next to those of the scorpions, the bestinvestigated arthropod venoms are those of the
honeybee Apis melli/era and several wasp species.
Like all poisonous secretions examined in any
detail, the venoms of the Hymenoptera are found
to be complex mixtures of substances. Amongst
the low molecular weight compounds are biogenic amines (histamine, 5-hydroxytryptamine,
dopamine, adrenalin, noradrenalin, acetylcholine), phospholipids, sugars and free amino acids
[5, 55]. Electrophoresis distinguishes 25-40
polypeptides in the toxic secretions of different
Hymenoptera. Various enzymes are found
amongst the proteins. The phospholipase A2
which makes up 12 % of the dry weight of bee
venom is a basic polypeptide of 129 amino acids
of known sequence. Wasp venoms also contain phospholipases of the types Al and B [33,
55]. The hyaluronidase of bee and other hymenopteran venoms promotes the spread of the
toxic substances in the tissues [32, 55]. The
hymenoptera-venoms also include esterases, glycosidases and protease inhibitors [55]. Enzyme
proteins constitute approximately 13-15 % of the
dry weight of worker bee venom, whereas that of
the queen bee contains only traces of phospholipase and hyaluronidase.
The most investigated components of
hymenoptera-venoms are the bioactive peptides,
which, for example, constitute 50-60 % of the
dry weight of bee venom. On the basis of their
pharmacological effects, one can distinguish
above all haemolytic, neurotoxic and kinin-like
peptides; these are distributed quite irregularly
amongst the different hymenopteran groups. The
haemolytic melittin (Fig.9.4a) predominates in
bee venom; in contrast, there are no haemolytic
proteins in wasp venom but various kinins are
found, which are lacking in the bee (Fig. 9.3).
Melittin is a peptide of 26 amino acids with an
amidated C-terminus and an N-terminus which is
formylated in about 10% of the molecules. On
the extended molecule, a non-polar N-terminal
section of 20 amino acids and a very basic Cterminal section can be differentiated (Fig. 9.4a).
This structure relates to the unusually strong
interaction with lipid double membranes: melittin
has a haemolytic effect and reduces the surface
tension of water to a much greater extent than do
all other peptides. Solutions of low ionic strength
contain the monomer, whereas in higher ionic
strength solutions and in the poison reservoir the
venom is found as a tetramer with the form of a
double cross [67]. Species related to the honey
bee have somewhat modified sequences
(Fig. 9.4a). The sequence of prepro-melittin has
been determined by the analysis of mRNA from
honey-bee venom glands: it consists of 70 amino
acids, of which 1-21 form the signal sequence and
22-43 form the pro-sequence. Mature melittin
consists of amino acids 44-70, with the terminal
glycine taking part in the amidation of the Cterminus [73]. The most important neurotoxic
component of bee venom is apamin, a basic peptide of only 18 amino acids (Fig.9.4a). Melittin
itself has a weak degranulating and histaminereleasing activity on mammalian mast cells; a
much higher activity is shown by the mast-cell
degranulating peptide (MCD) , an extremely
basic peptide (pI = 12) with 22 amino acids, of
which none is acidic and no fewer than 7 are basic
(Fig.9.4a). Finally, bee venom contains small