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Fig. 1.3
Domain architectures of different NEF families As examples for Hsp110 and Grp170
proteins the yeast homologs Sse1p and Lhs1p are shown, respectively. Both consist of an N-ter-
minal nucleotide binding domain (NBD,
blue
), a ʲ-sandwich (ʲ-Dom,
green
) and a α-helix bundle
domain (α-Dom,
pale yellow
). SS indicates a signal sequence for ER import. The HspBP1/Sil
family proteins have characteristic Armadillo repeat folds (
orange
). All members of the BAG fam-
ily in humans, Bag1-6, contain C-terminal Hsp70-binding BAG domains (
red
), but have other-
wise divergent domain architecture. Bag5 has four additional BAG domains of unknown function.
Bag1 isoforms and the large Bag6 contain Ubiquitin-like domains (Ubl,
dark blue
), which might
associate with the regulatory particle of the 26S proteasome. Bag6 has furthermore two probable
domains, which have not yet been characterized further. Bag2 contains a coiled-coil dimerization
domain (CC,
orange
). Bag3 comprises multiple N-terminal sequence motifs, WW domains (WW,
yellow
), IPV sequence motifs (
brown
) and PXXP repeats (
pink
). Bag1 L and Bag6 have NLS
sequences (
light green
) for nuclear targeting
Oh et al.
1997
; Oh et al.
1999
). The molecular basis for this holdase activity is still
controversial. Canonical Hsp70 proteins stably interact with substrate proteins only
in the ADP state, enclosing hydrophobic peptide segments between ʲ-domain and
α-helix bundle. While Sse1p appears to have no intrinsic ATPase activity—bound
ATP survived in the crystallization experiments for weeks—ATPase stimulation by
J-domain proteins has been observed (Mattoo et al.
2013
; Raviol et al.
2006a
). Con-
sistently, binding of Sse1p and human Hsp105 to hydrophobic peptides has been re-
ported, although with a preference towards aromatic residues in contrast to canonical
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