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An evolutionary and proteomic search for human gamete recognition proteins that mediate zona pellucida dissolution

介导透明带溶解的人类配子识别蛋白的进化和蛋白质组学研究

基本信息

批准号：
10370974
负责人：
WILLIE J SWANSON
金额：
$ 22.93万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-22 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10370974
关键词：
3-Dimensional Address Affinity Binding Biochemical Bioinformatics Biological Assay Biology Characteristics Chemotaxis Classification Codon Nucleotides Complementary DNA Data Databases Detection Distant Egg Proteins Event Evolution Exploratory/Developmental Grant for Diagnostic Cancer Imaging Female Fertilization Frequencies Future Genes Genetic Genomics Germ Cells Goals Guanine + Cytosine Composition Homologous Gene Homologous Protein Human Human Genome Knock-out Length Mass Spectrum Analysis Measures Mediating Molecular Morphology Mus N Domain Oocytes Performance Protein Structure Initiative Proteins Proteome Proteomics RNA Splicing Reproduction Research Resources Specificity Sperm Capacitation Structure Surface Plasmon Resonance Technology Testing Testis Transcript Variant Zona Pellucida abalone algorithm training base egg env Gene Products experience extracellular genetic approach genomic data improved innovation lysin male mammalian genome molecular phenotype nanopore prediction algorithm predictive test reproductive sperm cell sperm protein three dimensional structure transcriptome transcriptome sequencing transcriptomics

项目摘要

Project Summary The identification of interacting male-female reproductive proteins is imperative for a molecular understanding of fertilization. The goal of this R21 proposal is to identify a set of human gamete recognition proteins using genomic and proteomic approaches, and then perform evolutionary guided computational bioinformatic searches for a homolog of abalone sperm lysin. It is known from three-dimensional protein crystallographic studies of the major proteins from the mammalian Zona Pellucida (ZP) and abalone Vitelline Envelope (VE) that they contain homologous ZP-N domains. Given the molecular homology of ZP-N domains and overall biochemical similarity of the egg coats, an obvious question to address is whether sperm use similar mechanisms (or homologous proteins) to generate a path through the egg coat. The dissolution of the abalone egg VE by the sperm protein lysin has been extensively characterized. However, it remains unknown how mammalian sperm penetrate egg coats, and no lysin homolog is currently identifiable in any mammalian genome. Our proposal address this question by (1) using long-read sequencing to generate deep coverage of full-length non-chimeric cDNAs for use in sperm proteomics, (2) using these resources as a database to perform detailed bioinformatic analyses aimed at generating a database of putative human gamete recognition proteins and identification of a human homolog of abalone sperm lysin and (3) functional tests of predicted protein's ability to disrupt the mouse ZP. If we identify a human sperm lysin, it will immediately open up new avenues of research into mammalian gamete recognition and how the human sperm passes the ZP. If we are unsuccessful at identifying a human lysin, we will have generated a valuable genomic and proteomic resource database for future studies of human sperm biology.

项目总结