Figure 2.
Figure 2. Structure of the DCoH -HNF-p1 complex. a, The DCoH
dimer (yellow and orange) binds the HNF-p1 dimer (light and dark
blue) with two helix 2 sequences of DCoH in contact with two
helix 1 sequences of HNF-p1. The two-fold rotation axes of the
dimers coincide (arrow). b, The bound HNF-p1 dimer (light and
dark blue) forms an antiparallel four-helix bundle. The view is
along the two-fold rotation axis (+) with the DCoH binding
surface in front. Seven Leu side chains in each monomer
stabilize the dimer and make contacts with DCoH. Red spheres
mark two residues mutated in MODY3 patients, Leu 12 and Gly 20.
The site of a third MODY3 mutation, Gly 31, occurs in the
disordered region of the chain beyond residue 30. c,
Electrostatic potential displayed on the surface of the
recognition helices of DCoH (red, <-2.5 kT/e; white, -2.5 to 2.5
kT/e; and blue, >2.5 kT/e). A stick representation of helix 1 of
the HNF-p1 dimer (light blue) is superimposed on the surface. d,
The corresponding electrostatic potential displayed on the
surface of the HNF-1 recognition
helices. A stick representation of the recognition helices of
the bound DCoH (yellow) is superimposed. The two surfaces in (c)
and (d) match through a 180° rotation about a central, vertical
axis. Complementary positive (DCoH) and negative (HNF-p1)
potentials are evident on the left and right edges of the two
interfaces. e, Interactions between DCoH (yellow and orange) and
HNF-p1 (light and dark blue), viewed along the DCoH helical
axes. Only half of each helix is shown, because the interactions
in the other half are identical. Hydrophobic residues forming
the core of the interface are displayed in gray. Side chains
within hydrogen bonding distance are connected by lines. DCoH
Glu 58' caps the N-terminus of the HNF-p1 helix 1, the Leu 8
amide, and forms a hydrogen bond with Ser 6. DCOH Lys 59' forms
a hydrogen bond to the C-terminus of the neighboring HNF-p1
helix, the carbonyl of Ser 19'.
The above figure is reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2000,
7,
744-748)
copyright 2000.
recognition
helices. A stick representation of the recognition helices of
the bound DCoH (yellow) is superimposed. The two surfaces in (c)
and (d) match through a 180° rotation about a central, vertical
axis. Complementary positive (DCoH) and negative (HNF-p1)
potentials are evident on the left and right edges of the two
interfaces. e, Interactions between DCoH (yellow and orange) and
HNF-p1 (light and dark blue), viewed along the DCoH helical
axes. Only half of each helix is shown, because the interactions
in the other half are identical. Hydrophobic residues forming
the core of the interface are displayed in gray. Side chains
within hydrogen bonding distance are connected by lines. DCoH
Glu 58' caps the N-terminus of the HNF-p1 helix 1, the Leu 8
amide, and forms a hydrogen bond with Ser 6. DCOH Lys 59' forms
a hydrogen bond to the C-terminus of the neighboring HNF-p1
helix, the carbonyl of Ser 19'.