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

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2021 · $229,308

## Abstract

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.

## Key facts

- **NIH application ID:** 10370974
- **Project number:** 1R21HD105025-01A1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** WILLIE J SWANSON
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $229,308
- **Award type:** 1
- **Project period:** 2021-09-22 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10370974

## Citation

> US National Institutes of Health, RePORTER application 10370974, An evolutionary and proteomic search for human gamete recognition proteins that mediate zona pellucida dissolution (1R21HD105025-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10370974. Licensed CC0.

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