title: Structural analysis of the intracellular domain of (pro)renin receptor fused to maltose-binding protein.
abstract: The (pro)renin receptor (PRR) is an important component of the renin-angiotensin system (RAS), which regulates blood pressure and cardiovascular function. The integral membrane protein PRR contains a large extracellular domain (∼310 amino acids), a single transmembrane domain (∼20 amino acids) and an intracellular domain (∼19 amino acids). Although short, the intracellular (IC) domain of the PRR has functionally important roles in a number of signal transduction pathways activated by (pro)renin binding. Meanwhile, together with the transmembrane domain and a small portion of the extracellular domain (∼30 amino acids), the IC domain is also involved in assembly of V(0) portion of the vacuolar proton-translocating ATPase (V-ATPase). To better understand structural and multifunctional roles of the PRR-IC, we report the crystal structure of the PRR-IC domain as maltose-binding protein (MBP) fusion proteins at 2.0Å (maltose-free) and 2.15Å (maltose-bound). In the two separate crystal forms having significantly different unit-cell dimensions and molecular packing, MBP-PRR-IC fusion protein was found to be a dimer, which is different with the natural monomer of native MBP. The PRR-IC domain appears as a relatively flexible loop and is responsible for the dimerization of MBP fusion protein. Residues in the PRR-IC domain, particularly two tyrosines, dominate the intermonomer interactions, suggesting a role for the PRR-IC domain in protein oligomerization.
authors.affiliation: Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824-1319, USA.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Gao
authors.forename: R
authors.initials: R
authors.lastname: Michael Garavito
mesh_terms: D018360:Crystallography, X-Ray; D006801:Humans; D008320:Maltose / Q000737:chemistry*; D058619:Maltose-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000737:chemistry* / Q000235:genetics; D014443:Tyrosine / Q000737:chemistry / Q000235:genetics; D025262:Vacuolar Proton-Translocating ATPases / Q000737:chemistry* / Q000235:genetics; D000093342:Prorenin Receptor
chemical_list: D008320:Maltose; D058619:Maltose-Binding Proteins; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D014443:Tyrosine; D025262:Vacuolar Proton-Translocating ATPases; C458319:ATP6AP2 protein, human; D000093342:Prorenin Receptor