Structures of PHR Domains from Mus musculus Phr1 (Mycbp2) Explain the Loss-of-Function Mutation (Gly1092 → Glu) of the C. elegans Ortholog RPM-1

Parthasarathy Sampathkumar; Sinem A Ozyurt; Stacy A Miller; Kevin T Bain; Marc E Rutter; Tarun Gheyi; Benjamin Abrams; Yingchun Wang; Shane Atwell; John G Luz; Devon A Thompson; Stephen R Wasserman; J. Spencer Emtage; Eun Chan Park; Christopher Rongo; Yishi Jin; Richard L Klemke; J. Michael Sauder; Stephen K Burley; Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

doi:10.1016/j.jmb.2010.02.017

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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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Structures of PHR Domains from Mus musculus Phr1 (Mycbp2) Explain the Loss-of-Function Mutation (Gly1092 → Glu) of the C. elegans Ortholog RPM-1

Parthasarathy Sampathkumar, Sinem A Ozyurt, Stacy A Miller, Kevin T Bain, Marc E Rutter, Tarun Gheyi, Benjamin Abrams, Yingchun Wang, Shane Atwell, John G Luz, …

Journal of molecular biology, Vol.397(4), pp.883-892

2010

DOI: https://doi.org/10.1016/j.jmb.2010.02.017

PMCID: PMC2881670

PMID: 20156452

Abstract

Mycbp2

PHR domain

Phr1

RPM-1

synaptic development and axon guidance

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 β sandwich fold composed of 11 antiparallel β-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.

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Title: Structures of PHR Domains from Mus musculus Phr1 (Mycbp2) Explain the Loss-of-Function Mutation (Gly1092 → Glu) of the C. elegans Ortholog RPM-1
Creators: Parthasarathy Sampathkumar - Eli Lilly and Company, Lilly Biotechnology Center, 10300 Campus Point Drive, Suite 200, San Diego, CA 92121, USA
Sinem A Ozyurt - Eli Lilly and Company, Lilly Biotechnology Center, 10300 Campus Point Drive, Suite 200, San Diego, CA 92121, USA
Stacy A Miller - Eli Lilly and Company, Lilly Biotechnology Center, 10300 Campus Point Drive, Suite 200, San Diego, CA 92121, USA
Kevin T Bain - Eli Lilly and Company, Lilly Biotechnology Center, 10300 Campus Point Drive, Suite 200, San Diego, CA 92121, USA
Marc E Rutter - Eli Lilly and Company, Lilly Biotechnology Center, 10300 Campus Point Drive, Suite 200, San Diego, CA 92121, USA
Tarun Gheyi - Eli Lilly and Company, Lilly Biotechnology Center, 10300 Campus Point Drive, Suite 200, San Diego, CA 92121, USA
Benjamin Abrams - Department of Molecular, Cell and Developmental Biology, Sinsheimer Laboratories, University of California, Santa Cruz, Santa Cruz, CA, USA
Yingchun Wang - Department of Pathology and Moores Cancer Center, University of California at San Diego, San Diego, CA 92093, USA
Shane Atwell - Eli Lilly and Company, Lilly Biotechnology Center, 10300 Campus Point Drive, Suite 200, San Diego, CA 92121, USA
John G Luz - Eli Lilly and Company, Lilly Biotechnology Center, 10300 Campus Point Drive, Suite 200, San Diego, CA 92121, USA
Devon A Thompson - Eli Lilly and Company, Lilly Biotechnology Center, 10300 Campus Point Drive, Suite 200, San Diego, CA 92121, USA
Stephen R Wasserman - LRL-CAT, Eli Lilly and Company, Advanced Photon Source, Argonne National Laboratory, Building 401, 9700 South Cass Avenue, Argonne, IL 60439, USA
J. Spencer Emtage - Eli Lilly and Company, Lilly Biotechnology Center, 10300 Campus Point Drive, Suite 200, San Diego, CA 92121, USA
Eun Chan Park - Department of Genetics, The Waksman Institute, Rutgers University, Piscataway, NJ, USA
Christopher Rongo - Department of Genetics, The Waksman Institute, Rutgers University, Piscataway, NJ, USA
Yishi Jin - Department of Molecular, Cell and Developmental Biology, Sinsheimer Laboratories, University of California, Santa Cruz, Santa Cruz, CA, USA
Richard L Klemke - Department of Pathology and Moores Cancer Center, University of California at San Diego, San Diego, CA 92093, USA
J. Michael Sauder - Eli Lilly and Company, Lilly Biotechnology Center, 10300 Campus Point Drive, Suite 200, San Diego, CA 92121, USA
Stephen K Burley - Eli Lilly and Company, Lilly Biotechnology Center, 10300 Campus Point Drive, Suite 200, San Diego, CA 92121, USA
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Publication Details: Journal of molecular biology, Vol.397(4), pp.883-892
Date published: 2010
Publisher: Elsevier Ltd
Academic Unit: Waksman Institute of Microbiology; Chemistry and Chemical Biology (SAS); Institute for Quantitative Biomedicine
Language: English
Resource Type: Journal article
Identifiers: 991031665218504646