Zona pellucida sperm-binding protein 2 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the ''ZP2''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

Function

The

zona pellucida The zona pellucida (plural zonae pellucidae, also egg coat or pellucid zone) is a specialized extracellular matrix that surrounds the plasma membrane of mammalian oocytes. It is a vital constitutive part of the oocyte. The zona pellucida first ...

is an extracellular matrix that surrounds the

oocyte An oocyte (, ), oöcyte, or ovocyte is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in a female fetus in the ovary during female gametogenesis. The female ...

and early embryo. It is composed primarily of three (mouse) or four (human)

glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...

s (ZP1-4) with various functions during fertilization and preimplantation development. The protein encoded by this gene is a structural component of the zona pellucida and functions in secondary binding and penetration of

acrosome The acrosome is an organelle that develops over the anterior (front) half of the head in the spermatozoa (sperm cells) of many animals including humans. It is a cap-like structure derived from the Golgi apparatus. In placental mammals the acrosome ...

-reacted

spermatozoa A spermatozoon (; also spelled spermatozoön; ; ) is a motile sperm cell, or moving form of the haploid cell that is the male gamete. A spermatozoon joins an ovum to form a zygote. (A zygote is a single cell, with a complete set of chromosomes, ...

. The nascent protein contains a

N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...

signal peptide A signal peptide (sometimes referred to as signal sequence, targeting signal, localization signal, localization sequence, transit peptide, leader sequence or leader peptide) is a short peptide (usually 16-30 amino acids long) present at the N-ter ...

sequence, a conserved ZP domain, a consensus

furin Furin is a protease, a proteolytic enzyme that in humans and other animals is encoded by the ''FURIN'' gene. Some proteins are inactive when they are first synthesized, and must have sections removed in order to become active. Furin cleaves these s ...

cleavage site, and a

C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...

transmembrane domain. It is hypothesized that furin cleavage results in release of the mature protein from the plasma membrane for subsequent incorporation into the zona pellucida matrix. However, the requirement for furin cleavage in this process remains controversial based on mouse studies. The sperm-binding domain on the ZP2 protein is necessary in both humans and mice for oocyte-sperm recognition and penetration of the zona pellucida. It is also responsible for the primary block to polyspermy in mammals. The oocyte has cortical granules peripherally located under the cortex that contain a proteolytic protein called ovastacin. After the sperm binds to ZP2, the cortical granules are exocytosed releasing ovastacin into the

perivitelline space The perivitelline space is the space between the zona pellucida and the cell membrane of an oocyte or fertilized ovum. In the slow block to polyspermy, the cortical granules released from the ovum are deposited in the perivitelline space. Polysac ...

. Ovastacin cleaves ZP2 at the N terminus, preventing more sperm from binding and penetrating the oocyte, thus hardening the zona pellucida. Ovastacin is only found in oocytes, and is part of the astacin family of metalloendoproteases. Female mice engineered without ovastacin showed that ZP2 was not cleaved after fertilization.

3D structure

The crystal structure of the sperm-binding domain of ZP2 at 0.95 Å resolution () showed that is shares the same ZP-N fold first identified in structures of

ZP3 Zona pellucida sperm-binding protein 3, also known as zona pellucida glycoprotein 3 (Zp-3) or the sperm receptor, is a ZP module-containing protein that in humans is encoded by the ''ZP3'' gene. ZP3 is the receptor in the zona pellucida which bin ...

(). This provided experimental evidence for the suggestion that the N-terminal region of ZP2 consists of three ZP-N repeats and revealed that - despite insignificant sequence identity - ZP2 is structurally similar to VERL, the vitelline envelope receptor for egg lysin of the mollusk

abalone Abalone ( or ; via Spanish , from Rumsen ''aulón'') is a common name for any of a group of small to very large marine gastropod molluscs in the family (biology), family Haliotidae. Other common name In biology, a common name of a taxon o ...

(). This established a link between invertebrate and vertebrate

fertilization Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Proce ...

by suggesting that, despite being separated by 600 million years of evolution, mollusk and human use a common protein fold to interact with sperm.

Function

3D structure

References

Further reading