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microvesicles) that differ from exosomes. This budding is driven by the spe-
cific interaction between a PSAP sequence of TSG101/VPS23 and
ARRDC1.
80
In addition to their role at the PM, ARRDC3 and ARRDC4 are asso-
ciated with endosomes and lysosomes, whereas TXNIP and ARRDC2 are
essentially nuclear.
84
3.2. ARTs in yeast and fungi
Despite the presence of a few GPCRs in yeast (three for
Saccharomyces
cerevisiae,
nine for
Schizosaccharomyces pombe
), no gene coding
b
-arrestins
can be found in these organisms. Instead, the
Saccharomyces
genome encodes
10 arrestin-related proteins also called ARTs.
10
ARTs share a central arrestin core with sometimes-long extensions on
either side, increasing their size up to about 1100 amino acids for the longest
members. The percentage of identity with a visual arrestin is around 10%
and this percentage rises maximally to about 20% when identities and
homologies are considered. Threading their structures with the PSIPRED
software (
http://bioinf.cs.ucl.ac.uk/psipred
)
indicates secondary structures
essentially organized as
b
-strands. They aligned with arrestin-clan proteins
with a
p
-value of 3
10
8
(Rim8 vs.
VPS26). The arrestin core of most ART proteins (9 of 10 ARTs) was
successfully modeled with the Phyre2 online software using the structures
of mammalian arrestins as templates (
Fig. 2.4
). The lower
b
-sheet of the
arrestin-N domain is, in general, poorly modeled in ARTs. In fact, ARTs
differ from genuine arrestins in the C-terminal portion of their arrestin core
that includes
b
-strand 20. As
b
-strand 20 contributes to the N domain, the
structure of ARTs could not be reliably modeled at this level.
As with ARRDCs, most ART proteins have been shown to serve as
scaffolds for E3 ubiquitin ligases through their WW domain-binding sites
and to participate in the endocytosis of PM transporters.
10,85,86
The paralogue of ART9, called PalF in
Aspergillus nidulans
(known as
Emericella nidulans
in its sexual reproductive stage), is involved in a pH sig-
naling pathway. The function of PalF is related to the endocytosis of the
7TM pH sensor PalH and is
10
8
(Rod1 vs.
b
-arrestin 2) or 5
regulated by phosphorylation and
left-slanted lines correspond to a predicted arrestin-C domain; vertical hatches corre-
spond to a predicted VPS26 domain. (B) Ribbon representation (generated with the
PyMOL software) of representative proteins of the human arrestin clan. Coloring goes
from blue N-terminus to red C-terminus.
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