Biochemical and structural characterization of apolipoprotein A-I binding protein, a novel phosphoprotein with a potential role in sperm capacitation
Biochemical and structural characterization of apolipoprotein A-I binding protein, a novel phosphoprotein with a potential role in sperm capacitation
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DOI：
10.1210/en.2007-0582
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发表时间：
2008-05-01
期刊：
影响因子：
4.8
通讯作者：
Herr, John C.
中科院分区：
文献类型：
--
作者：
Jha, Kula N.;Shumilin, Igor A.;Herr, John C.
精子在雌性生殖道中发生的使其具有受精能力的生理变化构成获能现象。从精子表面的胆固醇流出和蛋白激酶A（PKA）依赖的磷酸化在获能中起主要的调节作用，但这两种现象之间的联系是未知的。我们报告，载脂蛋白A-I结合蛋白（AI-BP）磷酸化下游PKA激活，定位于精子头部和尾部结构域，并从精子释放到媒体在体外获能。AI-BP与载脂蛋白A-I相互作用，载脂蛋白A-I是参与胆固醇转运的高密度脂蛋白的组分。晶体结构表明AI-BP同源二聚体的亚基具有Rossmann样折叠。蛋白质表面有一个大的两室空腔，里面排列着保守的残基。这个空腔可能构成一个活性位点，表明AI-BP具有酶的功能。AI-BP在精子中的存在、其通过PKA的磷酸化及其在获能期间的释放表明AI-BP在获能中起重要作用，可能提供蛋白磷酸化和胆固醇流出之间的联系。
The physiological changes that sperm undergo in the female reproductive tract rendering them fertilization-competent constitute the phenomenon of capacitation. Cholesterol efflux from the sperm surface and protein kinase A(PKA)-dependent phosphorylation play major regulatory roles in capacitation, but the link between these two phenomena is unknown. We report that apolipoprotein A-I binding protein (AI-BP) is phosphorylated downstream to PKA activation, localizes to both sperm head and tail domains, and is released from the sperm into the media during in vitro capacitation. AI-BP interacts with apolipoprotein A-I, the component of high-density lipoprotein involved in cholesterol transport. The crystal structure demonstrates that the subunit of the AI-BP homodimer has a Rossmann-like fold. The protein surface has a large two compartment cavity lined with conserved residues. This cavity is likely to constitute an active site, suggesting that AI-BP functions as an enzyme. The presence of AI-BP in sperm, its phosphorylation by PKA, and its release during capacitation suggest that AI-BP plays an important role in capacitation possibly providing a link between protein phosphorylation and cholesterol efflux.