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Figure 2.
Fig. 2. Structural elements and conservation of VHL,
ElonginC, and ElonginB. (A) Sequence of VHL demonstrating that
tumor-derived missense mutations are divided between the  and  domains of
VHL, whereas residues contacting ElonginC cluster in the domain
(40). The histogram represents 279 missense mutations in the
database (29). The six most frequently mutated amino acids are
labeled. Shaded squares above each residue describe the relative
solvent exposure of a residue in a hypothetical VHL monomer.
Blue boxes indicate residues that make hydrogen bonds or van der
Waals contacts with ElonginC. (B) Sequence identity between
human ElonginC and ElonginC homologs is indicated by yellow, and
identity between human ElonginC and human Skp1, aligned with the
program THREADER2, is indicated by green. Residues that make
hydrogen bonds or van der Waals contacts with VHL are indicated
by red and those contacting ElonginB by blue. Secondary
structure and solvent accessibility are as in (A). A disordered
segment in ElonginC is indicated with a dashed line and extended
insertions in the alignments are indicated by lines below the
sequence alignments. (C) Sequence identity between human
ElonginB and ElonginB homologs is indicated by yellow. Identity
between human ElonginB and human ubiquitin, which maps primarily
to hydrophobic core residues, is indicated by green. Residues
that make hydrogen bonds or van der Waals contacts with ElonginC
are indicated by blue. Secondary structure and solvent
accessibility are as in (A), and disordered segments in the
ElonginB structure are indicated with a dashed line. (D)
Close-up view of the - interface
of VHL. VHL amino acids are in yellow and those of ElonginC are
in cyan. White dashed lines indicate hydrogen bonds, red atoms
indicate oxygen and blue, nitrogen. A red circle with the letter
"M" indicates a residue that is one of the six most frequently
mutated in tumors.
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