Agriculture Reference
In-Depth Information
prefers (poly)Ub tails bound by lysine in position 63
(K-63)
and has a moderate
affinity to the Ub bound to the lysine residue in position 48 (Johansen and Lamark
2011
). The UBA domains serve to ensure transport of cargo to the appropriate
process (autophagy or UPS) (Raasi et al.
2005
). Deletion of UBA domains
completely inhibit the function of selective autophagy receptors since they are
unable to recognise and bind substrates for autophagy clearance (Seibenhener
et al.
2004
).
LIR Motif
The LIR (
L
C3-interacting
r
egion) motif is a short (eight amino acids) sequence
responsible for directly binding of the selective autophagy receptors to ATG8
proteins attached to autophagosomal membranes. Interaction between the LIR
motif of the receptor and the ATG8 proteins is crucial for targeting cargo for
degradation. In a typical LIR motif (X
1
X
2
X
3
W/F/YX
1
X
2
L/I/VX
3
) the hydro-
phobic amino acids (W, F or Y and L, I or V) are essential for binding and occupy
the W-site and L-site created on the surface of ATG8 proteins. Amino acids in
positions X
1,
X
2,
X
3,
X
1,
X
2,
X
3
are not crucial for interaction but they can
enhance the strength of binding, particularly if acidic residues (D or E) are located
at positions X
1,
X
2
and X
3
or X
1
(Noda et al.
2008
,
2010
; Yamaguchi
et al.
2010
; Johansen and Lamark
2011
). For the AtNBR1 protein, an established
LIR motif (VSEWDPIL) was identified in a strongly conserved region between the
UBA1 and UBA2 domains.
A high conservation of the interaction between autophagy receptors and ATG8
proteins has been revealed. In HeLa cells, AtNBR1 is sequestered into
autophagosomes when human GABARAP subfamily members are also over-
expressed, demonstrating high evolutionary conservation of the selective
autophagy pathway and high structural similarity of ATG8 proteins among differ-
ent kingdoms (Svenning et al.
2011
).
Nuclear Localisation Signals
Selective autophagy cargo receptors can be involved in several different pathways
in addition to autophagy. Human p62, for example, also transports substrates
designated for degradation to the proteasome and continuously shuttles between
cytoplasm and nucleus. Proteins larger than 40 kDa, such as p62, are actively
transported between these two cellular compartments and need nuclear import
and export signals. Both importins and exportins transfer cargo protein into the
nucleus or cytoplasm in cooperation with the nuclear pore complex. Nuclear
localization signals (NLS) and nuclear export signal (NES) are short well-described
sequences recognised by nuclear-cytosolic transport receptors. Two functional
