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PDBsum entry 2rb3
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Lipid binding protein
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PDB id
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2rb3
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References listed in PDB file
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Key reference
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Title
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Crystal structures of human saposins c andd: implications for lipid recognition and membrane interactions.
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Authors
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M.Rossmann,
R.Schultz-Heienbrok,
J.Behlke,
N.Remmel,
C.Alings,
K.Sandhoff,
W.Saenger,
T.Maier.
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Ref.
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Structure, 2008,
16,
809-817.
[DOI no: ]
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PubMed id
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Abstract
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Human saposins are essential proteins required for degradation of sphingolipids
and lipid antigen presentation. Despite the conserved structural organization of
saposins, their distinct modes of interaction with biological membranes are not
fully understood. We describe two crystal structures of human saposin C in an
"open" configuration with unusual domain swapped homodimers. This form of SapC
dimer supports the "clip-on" model for SapC-induced vesicle fusion. In addition,
we present the crystal structure of SapD in two crystal forms. They reveal the
monomer-monomer interface for the SapD dimer, which was confirmed in solution by
analytical ultracentrifugation. The crystal structure of SapD suggests that side
chains of Lys10 and Arg17 are involved in initial association with the preferred
anionic biological membranes by forming salt bridges with sulfate or phosphate
lipid headgroups.
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Figure 2.
Figure 2. Crystal Structure of SapD
(A) Proposed SapD
dimer formation. SapD dimers are formed by contacts between
hairpin turns connecting α2″, α3′ and N-termini of helices
α3′ of molecules B and C, red ellipse indicates local C2
axis. In triclinic SapD, sulfate ions (marked SO4) are bound by
Lys10 and Arg17 of molecules A, B, and C but not D. Tyr54
(iodinated in SapD-iodoTyr54), Phe4, and Phe50 (magenta) shield
the hydrophobic inner cavity.
(B) Sulfate binding sites
formed inter- and intramolecularly by Lys10 and Arg17 of SapD
molecules A and B. Electron density is contoured at 1.3 σ
level. The distance between the two sulfate sulfur atoms is 8.3
Å.
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Figure 3.
Figure 3. Crystal Structure of SapC
(A) SapC dimer
formation. In the SapC dimer, domains α1/α2′/α2″, and
α3′/α3″/α4 are swapped, monomers intertwine to form a
dimer, and the red ellipse indicates a local C2 axis.
(B)
Superimposition of the four SapC molecules. Atoms of residues
2–19 were used for superimposition (SapC+SDS: PDB ID: 1SN6;
hexagonal SapC: PDB ID: 2GTG; tetragonal and orthorhombic SapC:
this study). SapC undergoes remarkable bending at hinges
(arrows) that transform it from a compact closed configuration
with hydrophilic exterior (hexagonal SapC) to an open
configuration exposing hydrophobic residues for lipid and
membrane interaction.
(C) Schematic presentation of the
hinge-bending motion of SapC. The hinge is located between α1
and α2′ at Asn22. The angle is measured between Cα atoms of
Val3, Asn22, and Ser37.
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The above figures are
reprinted
by permission from Cell Press:
Structure
(2008,
16,
809-817)
copyright 2008.
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