4ACR

Crystal structure of N-glycosylated, C-terminally truncated human glypican-1

Summary for 4ACR

• Entry DOI: 10.2210/pdb4acr/pdb
• Related: 4AD7
• Descriptor: GLYPICAN-1, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: proteoglycan, glycosaminoglycans, heparan sulfate, helical bundle, glycoprotein, membrane protein
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cell membrane; Lipid-anchor, GPI-anchor; Extracellular side. Secreted glypican-1: Secreted, extracellular space: P35052
• Total number of polymer chains: 4
• Total formula weight: 216186.67

Authors

Svensson, G.,Awad, W.,Mani, K.,Logan, D.T. (deposition date: 2011-12-17, release date: 2012-02-22, Last modification date: 2024-11-20)

Primary citation

Svensson, G.,Awad, W.,Hakansson, M.,Mani, K.,Logan, D.T.
Crystal Structure of N-Glycosylated Human Glypican-1 Core Protein: Structure of Two Loops Evolutionarily Conserved in Vertebrate Glypican-1.
J.Biol.Chem., 287:14040-, 2012

PubMed Abstract: Glypicans are a family of cell-surface proteoglycans that regulate Wnt, hedgehog, bone morphogenetic protein, and fibroblast growth factor signaling. Loss-of-function mutations in glypican core proteins and in glycosaminoglycan-synthesizing enzymes have revealed that glypican core proteins and their glycosaminoglycan chains are important in shaping animal development. Glypican core proteins consist of a stable α-helical domain containing 14 conserved Cys residues followed by a glycosaminoglycan attachment domain that becomes exclusively substituted with heparan sulfate (HS) and presumably adopts a random coil conformation. Removal of the α-helical domain results in almost exclusive addition of the glycosaminoglycan chondroitin sulfate, suggesting that factors in the α-helical domain promote assembly of HS. Glypican-1 is involved in brain development and is one of six members of the vertebrate family of glypicans. We expressed and crystallized N-glycosylated human glypican-1 lacking HS and N-glycosylated glypican-1 lacking the HS attachment domain. The crystal structure of glypican-1 was solved using crystals of selenomethionine-labeled glypican-1 core protein lacking the HS domain. No additional electron density was observed for crystals of glypican-1 containing the HS attachment domain, and CD spectra of the two protein species were highly similar. The crystal structure of N-glycosylated human glypican-1 core protein at 2.5 Å, the first crystal structure of a vertebrate glypican, reveals the complete disulfide bond arrangement of the conserved Cys residues, and it also extends the structural knowledge of glypicans for one α-helix and two long loops. Importantly, the loops are evolutionarily conserved in vertebrate glypican-1, and one of them is involved in glycosaminoglycan class determination.

PubMed: 22351761
DOI: 10.1074/JBC.M111.322487

Experimental method

X-RAY DIFFRACTION (2.55 Å)