2QYP

Orthorhombic Crystal Structure of Human Saposin C Dimer in Open Conformation

Summary for 2QYP

• Entry DOI: 10.2210/pdb2qyp/pdb
• Descriptor: Proactivator polypeptide (1 entity in total)
• Functional Keywords: saposin, activator protein, sap, alternative splicing, disease mutation, gaucher disease, glycoprotein, gm2-gangliosidosis, lipid metabolism, lysosome, metachromatic leukodystrophy, sphingolipid metabolism, lipid binding protein
• Biological source: Homo sapiens (human)
• Cellular location: Lysosome: P07602
• Total number of polymer chains: 2
• Total formula weight: 20757.72

Authors

Rossmann, M.,Saenger, W.,Maier, T. (deposition date: 2007-08-15, release date: 2008-04-29, Last modification date: 2024-10-30)

Primary citation

Rossmann, M.,Schultz-Heienbrok, R.,Behlke, J.,Remmel, N.,Alings, C.,Sandhoff, K.,Saenger, W.,Maier, T.
Crystal structures of human saposins C and d: implications for lipid recognition and membrane interactions.
Structure, 16:809-817, 2008

PubMed 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.

PubMed: 18462685
DOI: 10.1016/j.str.2008.02.016

Experimental method

X-RAY DIFFRACTION (2.45 Å)