Spermadhesins: a new protein family. Facts, hypotheses and perspectives.
Spermadhesins are a novel family of secretory proteins expressed in the male genital tract of pig, horse and bull. They are major products of the seminal plasma and have been found to be peripherally associated to the sperm surface. The structure and function of spermadhesins have been thoroughly investigated in the pig, which exhibits the greatest diversity of members: AWN, AQN-1, AQN-2, PSP-I and PSP-II and its glycosylated isoforms. They are multifunctional proteins showing a range of ligand-binding abilities, e.g. carbohydrates, sulfated glycosaminoglycans, phospholipids and protease inhibitors, suggesting that they may be involved in different steps of fertilization. Isolated porcine spermadhesins bind the zona pellucida glycoproteins in a cation-dependent manner with a Kd in a low micromolar range, and AWN, AQN-1 and AQN-3 display similar binding affinity for glycoproteins containing Gal beta(1-3)-GalNAc and Gal beta(1-4)-GlcNAc sequences in O-linked and N-linked oligosaccharides, respectively. During sperm passage through the epididymis AQN-3 and AWN have been shown to bind tightly to the sperm surface by interaction with the phospholipids of the membrane bilayer. At ejaculation the spermadhesins form a protective coat around the sensitive acrosomal region of the sperm head, thus possibly preventing premature acrosome reaction. During in vitro capacitation most of these aggregated sperm adhesins are lost, with the exception of phospholipid-bound spermadhesins. AWN and AQN-3 may now serve as a primary receptor for the oocyte zona pellucida, thus contributing to initial binding and recognition between sperm and egg. The amino acid sequence of spermadhesins does not show any discernible similarity with known carbohydrate recognition domains (CRD). However, they belong to the superfamily of proteins with a CUB domain with a predicted all-beta structure. The crystal structure of the heterodimeric complex of the spermadhesins PSP-I/PSP-II has been solved, showing that the overall structure of both spermadhesins consists of a beta-sandwich with five (parallel and antiparallel) beta-strands. It is the first three-dimensional structure of a zona pellucida-binding protein and reveals the architecture of the CUB domain. The spermadhesins represent a novel class of lectins that may be involved in sequential steps of fertilization, at least in the pig.
Töpfer-Petersen
E
E
Institut für Reproduktionsmedizin, Tierärzttliche Hochschule Hannover, Germany.
Romero
A
A
Varela
P F
PF
Ekhlasi-Hundrieser
M
M
Dostàlovà
Z
Z
Sanz
L
L
Calvete
J J
JJ
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D006023:Glycoproteins / Q000502:physiology; D006801:Humans; D008297:Male; D029589:Seminal Plasma Proteins; D029607:Seminal Vesicle Secretory Proteins; D013094:Spermatozoa / Q000378:metabolism / Q000502:physiology*
D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D029589:Seminal Plasma Proteins; D029607:Seminal Vesicle Secretory Proteins; C074521:seminal vesicle secretory protein II, porcine; C425042:spermadhesin; C074520:seminal vesicle secretory protein 109, porcine