title: Dissecting the structural basis of MEIG1 interaction with PACRG.
abstract: The product of the meiosis-expressed gene 1 (MEIG1) is found in the cell bodies of spermatocytes and recruited to the manchette, a structure unique to elongating spermatids, by Parkin co-regulated gene (PACRG). This complex is essential for targeting cargo to the manchette during sperm flagellum assembly. Here we show that MEIG1 adopts a unique fold that provides a large surface for interacting with other proteins. We mutated 12 exposed and conserved amino acids and show that four of these mutations (W50A, K57E, F66A, Y68A) dramatically reduce binding to PACRG. These four amino acids form a contiguous hydrophobic patch on one end of the protein. Furthermore, each of these four mutations diminishes the ability of MEIG1 to stabilize PACRG when expressed in bacteria. Together these studies establish the unique structure and key interaction surface of MEIG1 and provide a framework to explore how MEIG1 recruits proteins to build the sperm tail.
authors.affiliation: Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA, 23298.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599.
authors.forename: Ninad M
authors.initials: NM
authors.lastname: Walavalkar
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599.
authors.forename: William A
authors.initials: WA
authors.lastname: Buchwald
authors.affiliation: Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA, 23298.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Teves
authors.affiliation: Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA, 23298.|School of Public Health, Wuhan University of Science and Technology, Wuhan, Hubei, 430065, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA, 23298.|School of Public Health, Wuhan University of Science and Technology, Wuhan, Hubei, 430065, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bilinovich
authors.affiliation: Department of Biochemistry &Molecular Biology, Virginia Commonwealth University, Richmond, VA, 23298.
authors.forename: Darrell L
authors.initials: DL
authors.lastname: Peterson
authors.affiliation: Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA, 23298.|Department of Biochemistry &Molecular Biology, Virginia Commonwealth University, Richmond, VA, 23298.
authors.forename: Jerome F
authors.initials: JF
authors.lastname: Strauss
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599.
authors.forename: David C
authors.initials: DC
authors.lastname: Williams
authors.affiliation: Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA, 23298.|Department of Biochemistry &Molecular Biology, Virginia Commonwealth University, Richmond, VA, 23298.
authors.forename: Zhibing
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008840:Microfilament Proteins; D008958:Models, Molecular; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D009154:Mutation; D019906:Nuclear Magnetic Resonance, Biomolecular; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D055550:Protein Stability; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins; D012997:Solvents; D013329:Structure-Activity Relationship
chemical_list: D018797:Cell Cycle Proteins; C500770:Meig1 protein, mouse; D008840:Microfilament Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; C471712:Pacrg protein, mouse; D010750:Phosphoproteins; D011506:Proteins; D011994:Recombinant Proteins; D012997:Solvents