3lc8
Crystal structure of the cytoplasmic tail of (pro)renin receptor as a MBP fusion (Maltose-free form)
Structural highlights
DiseaseRENR_HUMAN X-linked intellectual disability, Hedera type;X-linked parkinsonism-spasticity syndrome. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. Defects in ATP6AP2 may be involved in a glycosylation disorder with autophagic defects characterized by serum protein hypoglycosylation, immunodeficiency, liver disease, psychomotor impairment, and cutis laxa.[1] FunctionMALE_ECOLI Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides.RENR_HUMAN Multifunctional protein which functions as a renin, prorenin cellular receptor and is involved in the assembly of the lysosomal proton-transporting V-type ATPase (V-ATPase) and the acidification of the endo-lysosomal system (PubMed:12045255, PubMed:29127204, PubMed:30374053, PubMed:32276428). May mediate renin-dependent cellular responses by activating ERK1 and ERK2 (PubMed:12045255). By increasing the catalytic efficiency of renin in AGT/angiotensinogen conversion to angiotensin I, may also play a role in the renin-angiotensin system (RAS) (PubMed:12045255). Through its function in V-type ATPase (v-ATPase) assembly and acidification of the lysosome it regulates protein degradation and may control different signaling pathways important for proper brain development, synapse morphology and synaptic transmission (By similarity).[UniProtKB:Q9CYN9][2] [3] [4] [5] Publication Abstract from PubMedThe (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 ( approximately 310 amino acids), a single transmembrane domain ( approximately 20 amino acids) and an intracellular domain ( approximately 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 ( approximately 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 2.0A (maltose-free) and 2.15A (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. Structural analysis of the intracellular domain of (pro)renin receptor fused to maltose-binding protein.,Zhang Y, Gao X, Michael Garavito R Biochem Biophys Res Commun. 2011 Mar 21. PMID:21420935[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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