4GJQ: Crystal Structure Of Human Gltp Bound With 12:0 Monosulfatide (orthorhombic Form;two Subunits In Asymmetric Unit)

Human glycolipid transfer protein (hsGLTP) forms the prototypical GLTP fold and is characterized by a broad transfer selectivity for glycosphingolipids (GSLs). The GLTP mutation D48V near the `portal entrance' of the glycolipid binding site has recently been shown to enhance selectivity for sulfatides (SFs) containing a long acyl chain. Here, nine novel crystal structures of hsGLTP and the SF-selective mutant complexed with short-acyl-chain monoSF and diSF in different crystal forms are reported in order to elucidate the potential functional roles of lipid-mediated homodimerization. In all crystal forms, the hsGLTP-SF complexes displayed homodimeric structures supported by similarly organized intermolecular interactions. The dimerization interface always involved the lipid sphingosine chain, the protein C-terminus (C-end) and alpha-helices 6 and 2, but the D48V mutant displayed a `locked' dimer conformation compared with the hinge-like flexibility of wild-type dimers. Differences in contact angles, areas and residues at the dimer interfaces in the `flexible' and `locked' dimers revealed a potentially important role of the dimeric structure in the C-end conformation of hsGLTP and in the precise positioning of the key residue of the glycolipid recognition centre, His140. DeltaY207 and DeltaC-end deletion mutants, in which the C-end is shifted or truncated, showed an almost complete loss of transfer activity. The new structural insights suggest that ligand-dependent reversible dimerization plays a role in the function of human GLTP.
PDB ID: 4GJQDownload
MMDB ID: 110866
PDB Deposition Date: 2012/8/10
Updated in MMDB: 2013/06
Experimental Method:
x-ray diffraction
Resolution: 2  Å
Source Organism:
Similar Structures:
Biological Unit for 4GJQ: dimeric; determined by author and by software (PISA)
Molecular Components in 4GJQ
Label Count Molecule
Proteins (2 molecules)
Glycolipid Transfer Protein(Gene symbol: GLTP)
Molecule annotation
Chemicals (3 molecules)
* Click molecule labels to explore molecular sequence information.

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