Co-chaperones of the Mammalian Endoplasmic Reticulum - The Networking of Chaperones by Co-chaperones - page 184

Table 9.2 Properties of BiP and its co-chaperones and NEFs. We note that the given concentra-
tions refer to a suspension of rough microsomes, which was isolated from canine pancreas and
adjusted to a concentration of 1 equivalent/ﾵl. In the ER lumen, the concentrations are approxi-
mately thousand-fold higher. The data were taken from Weitzmann et al. 2007 ; Zahedi et al. 2009 ).
GST glutathione-S-transferase
Protein UPR

controlled

Cellular
function(s)

Concentration
in suspension
of RM (ﾵM)

Recombi-
nant pro-
tein (amino
acid
residues)

Rate constants for inter-
action with BiP in the
presence of ATP
k a (M −1 s −1 ) k d (s −1 )

BiP + ERAD,

folding,
Sec61-gating,
transport,
UPR

5.00 BiP-

Hexahis
(20-655)

- -

ERj1 − Unknown 0.36 GST-J-

domain
(44-140)

6.00 ￗ 10 3 2.60 ￗ 10 −3

ERj2 − Transport 1.98 GST-J-

domain
(91-189)

0.81 ￗ 10 3 2.60 ￗ 10 −3

ERj3 + ERAD,

folding

0.29 GST-ERj3

(18-336)

1.25 ￗ 10 3 3.60 ￗ 10 −3

ERj4 +++ ERAD,

folding

Not detectable GST-ERj4

(23-222)

ERj5 + ERAD,

folding

2.00 GST-ERj5

(26-793)

6.20 ￗ 10 3 2.80 ￗ 10 −3

ERj6 + ERAD,

folding

Not
determined

GST-ERj6
(32-504)

64.4 3.97 ￗ 10 −3

ERj7 + Unknown 2.30 GST-J-

domain
(39-149)

5.07 ￗ 10 3 5.70 ￗ 10 −3

Grp170 + Folding, NEF 0.60 - Not

determined

Sil1 − NEF 0.005 GST-39-461 Not

detectable

Dong et al. 2008 ; Svard et al. 2011 ) may also play a role in substrate binding. Thus,
ERj3 through ERj6 are involved in protein folding under physiological as well as
stress conditions and in ERAD (Table 9.2 , Fig. 9.2 ). This is consistent with the fact
that these four BiP co-chaperones are over-produced together with BiP under stress
conditions, i.e. when there is an increased demand for chaperone and degradation
activity towards mis-folded polypeptides (Table 9.2 ). Therfore, it is not surprising
that these members of the resident ER Hsp70-cycle have been found in large com-
plexes with each other, with other chaperones and folding catalysts, and with other
resident ER proteins that are involved in N- or O-glycosylation (UDP-glucose-gly-
coprotein-glycosyltransferase or UGGT, SDF2L1) and calcium homeostasis (calu-
menin, reticulocalbin), respectively (Fig. 9.2 ).