Disulfide linkage patterns of pig zona pellucida glycoproteins ZP3 and ZP4

Kanai, Saeko; Kitayama, Tetsushi; Yonezawa, Naoto; Sawano, Yoriko; Tanokura, Masaru; Nakano, Minoru

doi:10.1002/mrd.20836

Cited by 18 publications

(24 citation statements)

References 26 publications

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“…S1D and S5A) also shares the same fold and disulfide connectivity of ZP3 and BG ZP-Cs (3,16,17) (Fig. S5 B and C), except for the C a -C b disulfide not found in ZP3 proteins (15) (Fig. S5D).…”

Section: E)mentioning

confidence: 75%

“…Type II contains 10 conserved Cys (C 1-7,a,b,8 ) and both homopolymerizes (UMOD, GP2, and TECTA) and heteropolymerizes (ZP1, ZP2, and ZP4), whereas type I (ZP3) includes eight conserved Cys (C [1][2][3][4][5][6][7][8] ) and only heteropolymerizes with type II (7,13,14). However, MS studies of egg coat protein disulfides are contradictory (15), and type II disulfide linkages C 5 -C 6 , C 7 -C a , and C b -C 8 are compatible neither with the fold of ZP3 (3) nor with structures of the ZP-C domain of BG, whose ZP module contains 10 Cys (16,17). At the same time, interpretation of the latter data in relation to polymerization is complicated by the fact that, like ENG, BG remains membrane-associated and does not form filaments (7,17).…”

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confidence: 99%

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A structured interdomain linker directs self-polymerization of human uromodulin

Bokhove

Nishimura

Brunati³

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

137

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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, saltdependent 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 α-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.uromodulin | ZP2 | polymerization | zona pellucida domain | X-ray crystallography U romodulin (UMOD) is expressed in the thick ascending limb of Henle's loop as a GPI membrane-anchored precursor that consists of three EGF-like domains, a domain of unknown function (D8C), and a zona pellucida (ZP) module (1, 2) (Fig. 1A, Top). The latter, containing Ig-like domains ZP-N and ZP-C (3-5), is found in other medically important human glycoproteins linked to infertility (egg coat components ZP1-ZP4), nonsyndromic deafness [inner ear α-and β-tectorin (TECTA/B)], Crohn's disease [glycoprotein 2 (GP2)], and cancer [TGF-β coreceptors betaglycan (BG) and endoglin (ENG)] (6, 7). Upon processing by Ser protease hepsin (8) at a consensus cleavage site (CCS) C-terminal to the ZP module (9), UMOD sheds a C-terminal propeptide (CTP) that contains a polymerization-blocking external hydrophobic patch (EHP), exposing an internal hydrophobic patch (IHP). This event triggers homopolymerization into filaments that are excreted into the urine (4, 10), where UMOD performs a plethora of biological functions, including protection against urinary tract infections, prevention of kidney stones, and activation of innate immunity (1,2,11,12).Although UMOD activity is strictly linked to its supramolecular state (2), the mechanism of ZP module-dependent assembly remains unclear. Mass spectroscopy (MS) analysis of ZP-C disulfide linkages suggests that there are two types of ZP modules with different structures (13). Type II contains 10 conserved Cys (C 1-7,a,b,8 ) and bo...

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Section: E)mentioning

confidence: 75%

mentioning

confidence: 99%

A structured interdomain linker directs self-polymerization of human uromodulin

Bokhove

Nishimura

Brunati³

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

137

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“…Gel proteins were transferred to nitrocellulose, which was blocked with 5% milk in Tris-buffered saline/Tween. Immunodetection was performed with goat polyclonal anti-pZP3 Ab (N- 20) and goat polyclonal anti-integrin β2 Ab (C-20), followed by incubation with donkey anti-goat HRP-conjugated Abs. The membranes were also incubated with anti-actin HRP-conjugated Ab (clone I-19; Santa Cruz Biotechnology, Santa Cruz, CA, USA) to ensure equal protein loading of the lanes.…”

Section: Sodium Dodecyl Sulfate-polyacrylamide Gel Electrophoresis (Smentioning

confidence: 99%

“…These ZPs genes are described in pigs as the porcine zona glycoproteins pZP1, pZP2, pZP3 and pZP3α. They are responsible for the major spermreceptor activity of the zona and play a significant role during fertilization [17][18][19][20].Integrins are major receptor proteins within the extracellular matrix (ECM) that mediate several functions connected with cell life and metabolism, such as cell adhesion, migration, cytoskeletal organization, proliferation, survival and differentiation. Several lines of experiments have identified the role of integrin β1 as a candidate molecule involved in sperm-oocyte interactions [21][22][23][24][25].…”

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confidence: 99%

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Follicular Size is Associated with the Levels of Transcripts and Proteins of Selected Molecules Responsible for the Fertilization Ability of Oocytes of Puberal Gilts

Antosik

Kempisty²,

Bukowska

et al. 2009

Journal of Reproduction and Development

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Abstract. The maturation and developmental competence of the oocyte is acquired during folliculogenesis. It is still unclear whether follicle size is associated with the levels of transcript and protein encoding molecules contributing to the fertilization ability of the porcine oocyte. Follicles were dissected from porcine ovaries after slaughter and classified as small (< 3 mm), medium (3-5 mm) or large (>5 mm), aspirated cumulus-oocyte complexes were cultured in standard porcine IVM culture medium (TCM 199) for 44 h. In developmentally competent oocytes, assessed by determining the activity of glucose-6-phosphate dehydrogenase (G6PDH) using a brilliant cresyl blue (BCB) test, real-time quantitative PCR reaction methods, western-blot and confocal microscopy analysis were applied to determine the transcript levels of porcine zona pellucida glycoproteins pZP1, pZP2, pZP3, pZP3 alpha and integrins beta 1 and beta 2, as well as the levels of pZP3 and integrin beta 2 proteins. We observed significantly higher levels of pZP1, pZP3 and integrin beta1 and beta2 transcripts in oocytes collected from medium follicles as compared with small follicles (P<0.001). Moreover, we found an increased content of all investigated mRNAs in oocytes isolated from large follicles as compared with small follicles (P<0.001). Western-blot analysis demonstrated a higher level of pZP3 protein in oocytes isolated from large and medium follicles as compared with small follicles (P<0.001). Our results suggest that the levels of transcripts and proteins for selected molecules contributing to the fertilization ability of oocytes are associated with follicular size in puberal gilts. Key words: Follicular size, Integrins, Oocyte, Pig, ZPs glycoproteins (J. Reprod. Dev. 55: [588][589][590][591][592][593] 2009) ocyte quality has a significant influence on early embryonic development and survival, establishment and maintenance of pregnancy, fetal development and even the health of offspring in postnatal life [1][2][3][4][5]. The developmental competence of an oocyte may be affected by follicle size [6][7][8]. The growth of the oocyte within the follicle is accompanied by expression of a series of genes [9][10][11]. Some of these genes are involved in cell cycle control and meiotic progression, resulting in full meiotic competence of the oocyte [12,13]. Several other proteins are involved in cellular progress as characterized by complete developmental competence of the gamete prior to fertilization [14,15]. During the growth phase, several messenger RNA (mRNA) and their respective proteins are accumulated and stored long-term to be used after fertilization and subsequent proper embryo development [1,16]. The abilities of fertilization and embryo development are acquired by an oocyte only after a long period of growth and development. Specific follicular growth and somatic follicular cell-oocyte interactions lead to the acquisition of high developmental potential for the oocyte.The porcine zona pellucida is composed of four major glycoproteins: ZP1...

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Posttranslational Modifications of Zona Pellucida Proteins

Yonezawa

2014

Advances in Experimental Medicine and Biology

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The zona pellucida (ZP), which surrounds the mammalian oocyte, functions in various aspects of fertilization. The ZP consists of three or four glycoproteins, which are derived from transmembrane proteins that lack the ability to self-assemble. Following posttranslational processing at specific sites, ectodomains of ZP precursor proteins are released from the membrane and begin to form a matrix. Glycosylational modification is thought to be involved in species-selective sperm recognition by ZP proteins. However, in mice, the supramolecular structure of the zona matrix is also important in sperm recognition. One ZP protein, ZP2, is processed at a specific site upon fertilization by ovastacin, which is released from cortical granules inside the oocyte. This phenomenon is involved in the block to polyspermy. The proteolysis of ubiquitinated ZP proteins by a sperm-associated proteasome is involved in penetration of the zona matrix by sperm, at least in the pigs. Thus, the posttranslational modification of ZP proteins is closely tied to ZP formation and the regulation of sperm-oocyte interactions.

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Disulfide linkage patterns of pig zona pellucida glycoproteins ZP3 and ZP4

Cited by 18 publications

References 26 publications

A structured interdomain linker directs self-polymerization of human uromodulin

A structured interdomain linker directs self-polymerization of human uromodulin

Follicular Size is Associated with the Levels of Transcripts and Proteins of Selected Molecules Responsible for the Fertilization Ability of Oocytes of Puberal Gilts

Posttranslational Modifications of Zona Pellucida Proteins

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