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PDBsum entry 2ffw
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References listed in PDB file
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Key reference
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Title
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Solution structure of the rbcc/trim b-Box1 domain of human mid1: b-Box with a ring.
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Authors
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M.A.Massiah,
B.N.Simmons,
K.M.Short,
T.C.Cox.
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Ref.
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J Mol Biol, 2006,
358,
532-545.
[DOI no: ]
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PubMed id
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Abstract
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B-box domains are a defining feature of the tripartite RBCC (RING, B-box,
coiled-coil) or TRIM proteins, many of which are E3 ubiquitin ligases. However,
little is known about the biological function of B-boxes. In some RBCC/TRIM
proteins there is only a single B-box (type 2) domain, while others have both
type 1 and type 2 B-box domains in tandem adjacent to their RING domain. These
two types of B-boxes share little sequence similarity, except the presence of
cysteine and histidine residues: eight in most B-box1 domains and seven in
B-box2 domains. We report here the high-resolution solution structure of the
first B-box1 domain (from the human RBCC protein, MID1) based on 670 nuclear
Overhauser effect (NOE)-derived distance restraints, 12 hydrogen bonds, and 44
dihedral angles. The domain consists of a three-turn alpha-helix, two short
beta-strands, and three beta-turns, encompassing Val117 to Pro164, which binds
two zinc atoms. One zinc atom is coordinated by cysteine residues 119, 122, 142,
145, while cysteine 134, 137 and histidine 150, 159 coordinate the other. This
topology is markedly different from the only other B-box structure reported;
that of a type 2 B-box from Xenopus XNF7, which binds a single zinc atom. Of
note, the B-box1 structure closely resembles the folds of the RING, ZZ and U-box
domains of E3 and E4 ubiquitin enzymes, raising the possibility that the B-box1
domain either has E3 activity itself or enhances the activity of RING type E3
ligases (i.e. confers E4 enzyme activity). The structure of the MID1 B-box1 also
reveals two potential protein interaction surfaces. One of these is likely to
provide the binding interface for Alpha 4 that is required for the localized
turnover of the catalytic subunit of PP2A, the major Ser/Thr phosphatase.
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Figure 5.
Figure 5. Surface representation of B-box1 showing basic
patches (colored blue) comprised of lysine and arginine
residues, acidic patches of glutamic and aspartic acids (colored
red), and hydrophobic surfaces (colored green) formed by
leucine, isoleucine, alanine, phenylalanine, and valine
residues. The red arrow indicates a cleft formed by two acidic
residues flanking a hydrophobic pocket. The blue arrow indicates
a large cleft of basic residues that may be important for
protein–protein interaction (possibly with Alpha 4).
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Figure 6.
Figure 6. Structural similarities between B-box1, RING,
U-box and ZZ domains. (a) Ribbon representation of RING domains
from the breast cancer susceptibility protein, BRCA1 (1JM7),
CDK-activating kinase assembly factor, MAT1 (1G25), a schematic
representation of a canonical RING structure, the U-box domain
from E4A, the ZZ domain from CBP/p300, and the B-box1 domain
from MID1. (b) Consensus zinc-binding motifs of RING, ZZ, U-box
and B-box1 domains; X=any amino acid, C and H are cysteine and
histidine, zinc-binding residues.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2006,
358,
532-545)
copyright 2006.
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