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PDBsum entry 1z2q
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Membrane protein
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PDB id
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1z2q
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References listed in PDB file
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Key reference
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Title
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A high-Resolution solution structure of a trypanosomatid fyve domain.
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Authors
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H.D.Mertens,
J.M.Callaghan,
J.D.Swarbrick,
M.J.Mcconville,
P.R.Gooley.
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Ref.
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Protein Sci, 2007,
16,
2552-2559.
[DOI no: ]
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PubMed id
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Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
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Abstract
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FYVE domain proteins play key roles in regulating membrane traffic in eukaryotic
cells. The FYVE domain displays a remarkable specificity for the head group of
the target lipid, phosphatidylinositol 3-phosphate (PtdIns[3]P). We have
identified five putative FYVE domain proteins in the genome of the protozoan
parasite Leishmania major, three of which are predicted to contain a functional
PtdIns(3)P-binding site. The FYVE domain of one of these proteins, LmFYVE-1,
bound PtdIns(3)P in liposome-binding assays and targeted GFP to acidified late
endosomes/lysosomes in mammalian cells. The high-resolution solution structure
of its N-terminal FYVE domain (LmFYVE-1[1-79]) was solved by nuclear magnetic
resonance. Functionally significant clusters of residues of the LmFYVE-1 domain
involved in PtdIns(3)P binding and dependence on low pH for tight binding were
identified. This structure is the first trypanosomatid membrane trafficking
protein to be determined and has been refined to high precision and accuracy
using residual dipolar couplings.
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Figure 2.
FYVE domain of LmFYVE-1(1 --79). (A) Stereoview of LmFYVE-1(1
--79). (Blue) Structure refined against RDCs, (red) unrefined
structure. (B) Cartoon representation of LmFYVE-1(1 --79)
showing selected side chains. (C) Overlay of FYVE domain
structures. (Red) LmFYVE-1(1 --79), (yellow) EEA1(1347 --1410),
(purple) HRS(156 --218), (green) Vps27 (168 --230). (D) Overlay
of FYVE domain active site showing positioning of functional
residues. The EEA1-bound ITP ligand as observed in the EEA1
crystal structure is shown as a ball and stick model.
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Figure 3.
Heteronuclear NMR relaxation data. The longitudinal, R[1]
(A), and transverse, R[2] (B), autorelaxation rates, and
^1H-^15N NOE (C) for LmFYVE-1(1 --79) acquired at 500 MHz. Data
were collected in the absence (black circles) and presence (open
circles) of 1.5 mM PtdIns(3)P at a protein concentration of 0.5
mM. The sequence position of secondary structure elements is
indicated.
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The above figures are
reprinted
from an Open Access publication published by the Protein Society:
Protein Sci
(2007,
16,
2552-2559)
copyright 2007.
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