5bup

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== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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During growth of the ovarian follicle, the mammalian oocyte becomes surrounded by an acellular coat called the zona pellucida. Whether the zona pellucida originates from the oocyte, surrounding follicle cells, or both has remained an unresolved issue. In experiments described here, denuded and follicle-enclosed mouse oocytes at various stages of growth were isolated and cultured in vitro in the presence of either [(35)S]methionine or [(3)H]fucose in order to determine the site of synthesis of the three, recently identified, zona pellucida proteins, ZP1, ZP2, and ZP3 [Bleil, J. D. &amp; Wassarman, P. M. (1980) Dev. Biol., in press]. Approximately 1.5% of the [(35)S]methionine, and as much as 45% of the [(3)H]fucose, that was incorporated into trichloroacetic acid-insoluble material by denuded or follicle-enclosed oocytes during a 12-hr culture period was found associated with zonae pellucidae removed from the cultured oocytes. Incorporation of [(35)S]methionine into zona pellucida proteins was depressed to less than 1/50th when denuded oocytes were cultured in the presence of puromycin, and secretion of zona pellucida proteins by denuded oocytes was demonstrated by pulse-chase experiments. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis of [(35)S]methionine- and [(3)H]fucose-labeled proteins present in oocytes, zonae pellucidae, and follicle cells revealed that denuded oocytes synthesize and secrete zona pellucida proteins, whereas no evidence was obtained to suggest that follicle cells synthesize these proteins. Denuded oocytes, ranging in diameter from 48 to 68 mum, incorporated both [(35)S]methionine and [(3)H]fucose into zona pellucida proteins during culture in vitro, whereas zonae pellucidae removed from fully-grown oocytes (85 mum) were not radiolabeled to a significant extent. After culture of denuded or follicle-enclosed oocytes for 12 hr, more than 95% of the [(3)H]fucose incorporated into oocyte proteins was found in ZP1, ZP2, and ZP3, indicating that the zona pellucida proteins are the major class of proteins glycosylated during oocyte growth. These results provide biochemical evidence supporting the idea that the zona pellucida originates from the mammalian oocyte itself, rather than from the surrounding follicle cells.
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Uromodulin (UMOD)/Tamm-Horsfall protein, the most abundant human urinary protein, plays a key role in chronic kidney diseases and is a promising therapeutic target for hypertension. Via its bipartite zona pellucida module (ZP-N/ZP-C), UMOD forms extracellular filaments that regulate kidney electrolyte balance and innate immunity, as well as protect against renal stones. Moreover, salt-dependent aggregation of UMOD filaments in the urine generates a soluble molecular net that captures uropathogenic bacteria and facilitates their clearance. Despite the functional importance of its homopolymers, no structural information is available on UMOD and how it self-assembles into filaments. Here, we report the crystal structures of polymerization regions of human UMOD and mouse ZP2, an essential sperm receptor protein that is structurally related to UMOD but forms heteropolymers. The structure of UMOD reveals that an extensive hydrophobic interface mediates ZP-N domain homodimerization. This arrangement is required for filament formation and is directed by an ordered ZP-N/ZP-C linker that is not observed in ZP2 but is conserved in the sequence of deafness/Crohn's disease-associated homopolymeric glycoproteins alpha-tectorin (TECTA) and glycoprotein 2 (GP2). Our data provide an example of how interdomain linker plasticity can modulate the function of structurally similar multidomain proteins. Moreover, the architecture of UMOD rationalizes numerous pathogenic mutations in both UMOD and TECTA genes.
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Synthesis of zona pellucida proteins by denuded and follicle-enclosed mouse oocytes during culture in vitro.,Bleil JD, Wassarman PM Proc Natl Acad Sci U S A. 1980 Feb;77(2):1029-33. PMID:6928658<ref>PMID:6928658</ref>
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A structured interdomain linker directs self-polymerization of human uromodulin.,Bokhove M, Nishimura K, Brunati M, Han L, de Sanctis D, Rampoldi L, Jovine L Proc Natl Acad Sci U S A. 2016 Jan 25. pii: 201519803. PMID:26811476<ref>PMID:26811476</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

Revision as of 09:02, 10 February 2016

Crystal structure of the ZP-C domain of mouse ZP2

5bup, resolution 2.25Å

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