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PDBsum entry 2qyp

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protein Protein-protein interface(s) links
Lipid binding protein PDB id
2qyp
Jmol
Contents
Protein chains
78 a.a. *
81 a.a. *
* Residue conservation analysis
PDB id:
2qyp
Name: Lipid binding protein
Title: Orthorhombic crystal structure of human saposin c dimer in open conformation
Structure: Proactivator polypeptide. Chain: a, b. Fragment: saposin-c domain. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: psap, glba, sap1. Expressed in: pichia pastoris. Expression_system_taxid: 4922.
Resolution:
2.45Å     R-factor:   0.232     R-free:   0.290
Authors: M.Rossmann,W.Saenger,T.Maier
Key ref:
M.Rossmann et al. (2008). Crystal structures of human saposins C andD: implications for lipid recognition and membrane interactions. Structure, 16, 809-817. PubMed id: 18462685 DOI: 10.1016/j.str.2008.02.016
Date:
15-Aug-07     Release date:   29-Apr-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P07602  (SAP_HUMAN) -  Prosaposin
Seq:
Struc:
 
Seq:
Struc:
524 a.a.
78 a.a.
Protein chain
Pfam   ArchSchema ?
P07602  (SAP_HUMAN) -  Prosaposin
Seq:
Struc:
 
Seq:
Struc:
524 a.a.
81 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     lysosome   1 term 
  Biological process     lipid metabolic process   2 terms 

 

 
DOI no: 10.1016/j.str.2008.02.016 Structure 16:809-817 (2008)
PubMed id: 18462685  
 
 
Crystal structures of human saposins C andD: implications for lipid recognition and membrane interactions.
M.Rossmann, R.Schultz-Heienbrok, J.Behlke, N.Remmel, C.Alings, K.Sandhoff, W.Saenger, T.Maier.
 
  ABSTRACT  
 
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.
 
  Selected figure(s)  
 
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.
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.
 
  The above figures are reprinted by permission from Cell Press: Structure (2008, 16, 809-817) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21463581 S.Baoukina, and D.P.Tieleman (2011).
Lung surfactant protein SP-B promotes formation of bilayer reservoirs from monolayer and lipid transfer between the interface and subphase.
  Biophys J, 100, 1678-1687.  
  20110733 A.Almlén, F.J.Walther, A.J.Waring, B.Robertson, J.Johansson, and T.Curstedt (2010).
Synthetic surfactant based on analogues of SP-B and SP-C is superior to single-peptide surfactants in ventilated premature rabbits.
  Neonatology, 98, 91-99.  
20498017 B.R.Pearse, T.Tamura, J.C.Sunryd, G.A.Grabowski, R.J.Kaufman, and D.N.Hebert (2010).
The role of UDP-Glc:glycoprotein glucosyltransferase 1 in the maturation of an obligate substrate prosaposin.
  J Cell Biol, 189, 829-841.  
20179319 M.Abdul-Hammed, B.Breiden, M.A.Adebayo, J.O.Babalola, G.Schwarzmann, and K.Sandhoff (2010).
Role of endosomal membrane lipids and NPC2 in cholesterol transfer and membrane fusion.
  J Lipid Res, 51, 1747-1760.  
19298372 M.R.Beck, G.T.Dekoster, D.P.Cistola, and W.E.Goldman (2009).
NMR structure of a fungal virulence factor reveals structural homology with mammalian saposin B.
  Mol Microbiol, 72, 344-353.
PDB code: 2jv7
19258449 V.Parkash, P.Lindholm, J.Peränen, N.Kalkkinen, E.Oksanen, M.Saarma, V.M.Leppänen, and A.Goldman (2009).
The structure of the conserved neurotrophic factors MANF and CDNF explains why they are bifunctional.
  Protein Eng Des Sel, 22, 233-241.
PDB codes: 2w50 2w51
18783340 Y.Kacher, B.Brumshtein, S.Boldin-Adamsky, L.Toker, A.Shainskaya, I.Silman, J.L.Sussman, and A.H.Futerman (2008).
Acid beta-glucosidase: insights from structural analysis and relevance to Gaucher disease therapy.
  Biol Chem, 389, 1361-1369.
PDB code: 2vt0
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.