3Q2U

Structure of Human Glioma Pathogenesis-related Protein 1 Reveals Unique loops and surface motifs.

Summary for 3Q2U

• Entry DOI: 10.2210/pdb3q2u/pdb
• Related: 1U53 3Q2R
• Descriptor: Glioma pathogenesis-related protein 1, GLYCEROL (3 entities in total)
• Functional Keywords: crisp, human glioma pathogenesis-related protein 1 (glipr1), rtvp1, membrane protein
• Biological source: Homo sapiens (human)
• Cellular location: Membrane ; Single-pass membrane protein : P48060
• Total number of polymer chains: 1
• Total formula weight: 23691.68

Authors

Asojo, O.A. (deposition date: 2010-12-20, release date: 2011-10-05, Last modification date: 2024-10-16)

Primary citation

Asojo, O.A.,Koski, R.A.,Bonafe, N.
Structural studies of human glioma pathogenesis-related protein 1.
Acta Crystallogr.,Sect.D, 67:847-855, 2011

PubMed Abstract: Human glioma pathogenesis-related protein 1 (GLIPR1) is a membrane protein that is highly upregulated in brain cancers but is barely detectable in normal brain tissue. GLIPR1 is composed of a signal peptide that directs its secretion, a conserved cysteine-rich CAP (cysteine-rich secretory proteins, antigen 5 and pathogenesis-related 1 proteins) domain and a transmembrane domain. GLIPR1 is currently being investigated as a candidate for prostate cancer gene therapy and for glioblastoma targeted therapy. Crystal structures of a truncated soluble domain of the human GLIPR1 protein (sGLIPR1) solved by molecular replacement using a truncated polyalanine search model of the CAP domain of stecrisp, a snake-venom cysteine-rich secretory protein (CRISP), are presented. The correct molecular-replacement solution could only be obtained by removing all loops from the search model. The native structure was refined to 1.85 Å resolution and that of a Zn2+ complex was refined to 2.2 Å resolution. The latter structure revealed that the putative binding cavity coordinates Zn2+ similarly to snake-venom CRISPs, which are involved in Zn2+-dependent mechanisms of inflammatory modulation. Both sGLIPR1 structures have extensive flexible loop/turn regions and unique charge distributions that were not observed in any of the previously reported CAP protein structures. A model is also proposed for the structure of full-length membrane-bound GLIPR1.

PubMed: 21931216
DOI: 10.1107/S0907444911028198

Experimental method

X-RAY DIFFRACTION (1.85 Å)