PDBsum entry 2rb3

Lipid binding protein

PDB id: 2rb3

Contents

Protein chains

79 a.a. *

Ligands

SO4 ×3

GOL ×2

Waters ×381

* Residue conservation analysis

PDB id:

2rb3

Name:

Lipid binding protein

Title:

Crystal structure of human saposin d

Structure:

Proactivator polypeptide. Chain: a, b, c, d. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: psap, glba, sap1. Expressed in: pichia pastoris. Expression_system_taxid: 4922.

Resolution:

2.10Å R-factor: 0.214 R-free: 0.274

Authors:

T.Maier,M.Rossman,W.Saenger

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:

18-Sep-07 Release date: 29-Apr-08

Protein chains

P07602  (SAP_HUMAN) -  Prosaposin from Homo sapiens

Seq: 524 a.a.

Struc: 79 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

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.