4GHP

Crystal Structure of D48V||A47D mutant of Human GLTP bound with 12:0 monosulfatide

Summary for 4GHP

• Entry DOI: 10.2210/pdb4ghp/pdb
• Related: 3RIC 4GH0 4GHS
• Descriptor: Glycolipid transfer protein, N-{(2S,3R,4E)-3-hydroxy-1-[(3-O-sulfo-beta-D-galactopyranosyl)oxy]octadec-4-en-2-yl}dodecanamide (3 entities in total)
• Functional Keywords: gltp-fold, lipid transport
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q9NZD2
• Total number of polymer chains: 1
• Total formula weight: 24629.83

Authors

Samygina, V.R.,Ochoa-Lizarralde, B.,Popov, A.N.,Malinina, L. (deposition date: 2012-08-08, release date: 2013-04-10, Last modification date: 2023-11-08)

Primary citation

Samygina, V.R.,Ochoa-Lizarralde, B.,Popov, A.N.,Cabo-Bilbao, A.,Goni-de-Cerio, F.,Molotkovsky, J.G.,Patel, D.J.,Brown, R.E.,Malinina, L.
Structural insights into lipid-dependent reversible dimerization of human GLTP.
Acta Crystallogr.,Sect.D, 69:603-616, 2013

PubMed Abstract: 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 α-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. ΔY207 and ΔC-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.

PubMed: 23519669
DOI: 10.1107/S0907444913000024

Experimental method

X-RAY DIFFRACTION (1.9 Å)