J Michael Sauder - Structures of PHR domains from Mus musculus Phr1 (Mycbp2) explain the loss-of-function mutation (Gly1092-->Glu) of the C. elegans ortholog RPM-1

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      Publication Details (including relevant citation   information):

      J Mol Biol (2010) 397:883-892.

      Sampathkumar P, Ozyurt SA, Miller SA, Bain KT, Rutter ME, Gheyi   T, Abrams B, Wang Y, Atwell S, Luz JG, Thompson DA, Wasserman SR,   Emtage JS, Park EC, Rongo C, Jin Y, Klemke RL, Sauder JM, Burley   SK


      PHR [PAM (protein associated with Myc)-HIW (Highwire)-RPM-1   (regulator  of presynaptic morphology 1)] proteins are   conserved, large multi-domain  E3 ubiquitin ligases with   modular architecture. PHR proteins  presynaptically control   synaptic growth and axon guidance and  postsynaptically   regulate endocytosis of glutamate receptors.  Dysfunction of   neuronal ubiquitin-mediated proteasomal degradation is    implicated in various neurodegenerative diseases. PHR proteins   are  characterized by the presence of two PHR domains near   the N-terminus,  which are essential for proper localization   and function. Structures of  both the first and second PHR   domains of Mus musculus (mouse) Phr1 (MYC  binding protein   2, Mycbp2) have been determined, revealing a novel beta    sandwich fold composed of 11 antiparallel beta-strands. Conserved   loops  decorate the apical side of the first PHR domain   (MmPHR1), yielding a  distinct conserved surface feature.   The surface of the second PHR domain  (MmPHR2), in contrast,   lacks significant conservation. Importantly, the  structure   of MmPHR1 provides insights into a loss-of-function   mutation,  Gly1092-->Glu, observed in the Caenorhabditis   elegans ortholog  RPM-1.

      Address (URL): http://www.ncbi.nlm.nih.gov/pubmed/20156452