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PDBsum entry 1m6b
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Signaling protein, transferase
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PDB id
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1m6b
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structure of the extracellular region of her3 reveals an interdomain tether.
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Authors
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H.S.Cho,
D.J.Leahy.
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Ref.
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Science, 2002,
297,
1330-1333.
[DOI no: ]
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PubMed id
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Abstract
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We have determined the 2.6 angstrom crystal structure of the entire
extracellular region of human HER3 (ErbB3), a member of the epidermal growth
factor receptor (EGFR) family. The structure consists of four domains with
structural homology to domains found in the type I insulin-like growth factor
receptor. The HER3 structure reveals a contact between domains II and IV that
constrains the relative orientations of ligand-binding domains and provides a
structural basis for understanding both multiple-affinity forms of EGFRs and
conformational changes induced in the receptor by ligand binding during
signaling. These results also suggest new therapeutic approaches to modulating
the behavior of members of the EGFR family.
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Figure 2.
Fig. 2. The domain II/IV contact. (A) Side chains of residues
that mediate contacts between domain II (green) and domain IV
(red) are shown. Hydrogen bonds and salt bridges are indicated
by dashed lines. This figure was made with MOLSCRIPT (36). (B)
Alignment of human ErbB receptor sequences from the domain II/IV
contact regions. Residues with direct contacts to one another in
sHER3 are highlighted in similar colors. Pro593 and Phe^595 of
HER2, which fail to conserve the pattern of contact residues,
are underlined.
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Figure 3.
Fig. 3. Surface representations of sHER3 and EGF (32). sHER3 is
rotated ~180° about a vertical axis relative to its
orientation in Fig. 1A. EGF and the sites in sHER3 (Y104 and
V333) homologous to the sites in HER1 to which EGF cross-links
(30, 31) are in red. Domains I to IV and the domain II/IV
connection are labeled. This figure was made with the program
GRASP (37).
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The above figures are
reprinted
by permission from the AAAs:
Science
(2002,
297,
1330-1333)
copyright 2002.
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