Memo is homologous to nonheme iron dioxygenases and binds an ErbB2-derived phosphopeptide in its vestigial active site.
Memo (mediator of ErbB2-driven cell motility) is a 297-amino-acid protein recently shown to co-precipitate with the C terminus of ErbB2 and be required for ErbB2-driven cell motility. Memo is not homologous to any known signaling proteins, and how it mediates ErbB2 signals is not known. To provide a molecular basis for understanding Memo function, we have determined and report here the 2.1A crystal structure of human Memo and show it be homologous to class III nonheme iron-dependent dioxygenases, a structural class that now includes a zinc-binding protein of unknown function. No metal binding or enzymatic activity can be detected for Memo, but Memo does bind directly to a specific ErbB2-derived phosphopeptide encompassing Tyr-1227 using its vestigial enzymatic active site. Memo thus represents a new class of phosphotyrosine-binding protein.
Qiu
Chen
C
Department of Biophysics and Biophysical Chemistry, The Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
Lienhard
Susanne
S
Hynes
Nancy E
NE
Badache
Ali
A
Leahy
Daniel J
DJ
D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D002465:Cell Movement / Q000502:physiology; D018360:Crystallography, X-Ray; D006801:Humans; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019159:Nonheme Iron Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010748:Phosphopeptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019000:Phosphotyrosine / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D047908:Intracellular Signaling Peptides and Proteins; D019159:Nonheme Iron Proteins; D010748:Phosphopeptides; D019000:Phosphotyrosine; D018719:Erb-b2 Receptor Tyrosine Kinases; D011994:Recombinant Proteins; C527585:MEMO1 protein, human; C508053:ERBB2 protein, human