Biology Reference
In-Depth Information
to a fuller understanding of what NPAs do. The question is most pertinent
in parasitic nematodes if NPAs are released by the parasites into the
tissues they occupy (although this is not thought to be the case for
Globodera pallida,
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in which case another group of unusual lipid binding
proteins released by nematodes, the FAR proteins, may be important).
95,96
One possibility that is often raised, albeit so far untested, is that NPAs
could be involved in interacting with host cells by delivering pharma-
cologically active lipids, or sequestering those produced by the host (such
as retinol, platelet activating factor, eicosanoids such as arachidonic acid
and leukotrienes, all of which they appear to bind
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) in order to modulate
local and systemic immune and inflammatory responses. These ideas are
difficult to test, and remain to be addressed, as with other lipid binding
proteins released by nematode parasites, but knowledge of NPA struc-
tures should facilitate the design of mutant proteins that do not bind
selected lipids.
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AN UNUSUAL LIPID BINDING PROTEIN IN THE
PERIVITELLINE FLUID OF
ASCARIS
EGGS
Most of this chapter has dealt with proteins of direct relevance to
immune responses to Ascaris, and the structure of its major allergen, but
structures of other interesting proteins are now emerging. These include
an unusual protein found in the perivitelline fluid of the eggs of Ascaris
(the fluid surrounding the developing larva),
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which may be involved in
maintenance of the lipid layer of the shell (e.g. by removing and replacing
oxidized lipids), scavenging lipids in the fluid itself, or in maintaining the
lipid balance within the whole egg/larva system. This is As-p18, which
also has homologues in the periviteline fluid of other species of nematode,
such as the agent of lymphatic filariasis Brugia malayi.
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When originally
sequenced, it was clear that As-p18 is a member of a family of small lipid
binding proteins that is ubiquitous in the animal phyla, but also that it has
unusual features that had not been found before. This family is the
cytosolic lipid binding proteins such as the nine fatty acid binding
proteins (FABPs), and the cellular retinol and retinoic acid binding
proteins (CRBPs, CRABPs) of humans.
99,100
These are thought to have
many functions inside cells, including central involvement in transport of
lipids into and out of cells, maintaining the balance of lipid stores, and
transporting small lipids involved in cell
cell signaling in regulating
cellular activation and differentiation. Such proteins are needed because
the lipids involved are relatively insoluble, potentially damaging to
cellular membranes, and in need of protection from chemical damage, the
latter applying to signaling lipids in particular. The structures of these
proteins from mammals are well known, and all of them are so similar as
e
