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Figure 2.
Figure 2. The CARP2 FYVE-Type Domain Has Several Unique
Structural Features(A) Comparison of the CARP2 FYVE-type domain
with the EEA1 FYVE domain and the Rabphilin-3A FYVE-related
domain. Several distinguishing structural features are
highlighted, including the phosphoinositide binding pocket for
EEA1, the b3-b4 loop, the membrane insertion tip, and the
distinct kink in the loop close to the binding pocket in CARP2.
Details of the membrane insertion region of all three proteins
are shown in the inset. The CARP2 tip region lacks the
hydrophobic property that is conserved in EEA1 and
Rabphilin-3A.(B) A stereo view of the membrane insertion loop of
CARP2. The 2Fo-Fc electron density map, colored magenta and
contoured at 1.2 s, is shown at the tip of membrane insert loop.
The three amino acid residues at the tip, Ala55, Asn56, and
Thr57, are labeled.(C) Sequence alignment of the FYVE-type
domains from CARP2, CARP1, Fgd1, Vps27p, Hrs, EEA1, SARA,
Rabphilin-3A, and NOC2. The alignment highlights the
conservation of the zinc-coordinating cysteines and key sequence
differences between the different subfamilies of FYVE-type
domains. Note that the WxxD motif is conserved only in
phosphoinositide binding FYVE domains. The solid line identifies
the R(R/K)HHCR signature motif, and the double line indicates
the C-terminal RVC motif. The membrane insertion tip residues
are indicated by a wavy line. The eight conserved cysteines that
coordinate two zinc atoms are indicated with asterisks. The
conserved glycine in FYVE domains is indicated by a yellow box,
and the conserved glycine in FYVE-related domains is indicated
by a blue triangle.
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