5GMI

Crystal Structure of GRASP55 GRASP domain in complex with JAM-C C-terminus

Summary for 5GMI

• Entry DOI: 10.2210/pdb5gmi/pdb
• Related: 5GMJ 5GML
• Descriptor: Golgi reassembly-stacking protein 2, Junctional adhesion molecule C (3 entities in total)
• Functional Keywords: beta strand sandswish, classic pdz peptide binding groove, conserved carboxylate-binding loop, structural protein-peptide complex, structural protein/peptide
• Biological source: Mus musculus (Mouse); More
• Cellular location: Golgi apparatus membrane ; Lipid-anchor : Q99JX3; Cell membrane ; Single-pass type I membrane protein : Q9D8B7
• Total number of polymer chains: 4
• Total formula weight: 56469.04

Authors

Shi, N.,Shi, X.,Morelli, X.,Betzi, S.,Huang, X. (deposition date: 2016-07-14, release date: 2017-05-24, Last modification date: 2023-11-08)

Primary citation

Cartier-Michaud, A.,Bailly, A.L.,Betzi, S.,Shi, X.,Lissitzky, J.C.,Zarubica, A.,Serge, A.,Roche, P.,Lugari, A.,Hamon, V.,Bardin, F.,Derviaux, C.,Lembo, F.,Audebert, S.,Marchetto, S.,Durand, B.,Borg, J.P.,Shi, N.,Morelli, X.,Aurrand-Lions, M.
Genetic, structural, and chemical insights into the dual function of GRASP55 in germ cell Golgi remodeling and JAM-C polarized localization during spermatogenesis
PLoS Genet., 13:e1006803-e1006803, 2017

PubMed Abstract: Spermatogenesis is a dynamic process that is regulated by adhesive interactions between germ and Sertoli cells. Germ cells express the Junctional Adhesion Molecule-C (JAM-C, encoded by Jam3), which localizes to germ/Sertoli cell contacts. JAM-C is involved in germ cell polarity and acrosome formation. Using a proteomic approach, we demonstrated that JAM-C interacted with the Golgi reassembly stacking protein of 55 kDa (GRASP55, encoded by Gorasp2) in developing germ cells. Generation and study of Gorasp2-/- mice revealed that knock-out mice suffered from spermatogenesis defects. Acrosome formation and polarized localization of JAM-C in spermatids were altered in Gorasp2-/- mice. In addition, Golgi morphology of spermatocytes was disturbed in Gorasp2-/- mice. Crystal structures of GRASP55 in complex with JAM-C or JAM-B revealed that GRASP55 interacted via PDZ-mediated interactions with JAMs and induced a conformational change in GRASP55 with respect of its free conformation. An in silico pharmacophore approach identified a chemical compound called Graspin that inhibited PDZ-mediated interactions of GRASP55 with JAMs. Treatment of mice with Graspin hampered the polarized localization of JAM-C in spermatids, induced the premature release of spermatids and affected the Golgi morphology of meiotic spermatocytes.

PubMed: 28617811
DOI: 10.1371/journal.pgen.1006803

Experimental method

X-RAY DIFFRACTION (2.71 Å)