Binding of recombinant human proacrosin/acrosin to zona pellucida (ZP) glycoproteins. I. Studies with recombinant human ZPA, ZPB, and ZPC

Fertil Steril. 2005 Jun;83(6):1780-90. doi: 10.1016/j.fertnstert.2004.12.042.

Abstract

Objective: To characterize proacrosin/acrosin interaction with isolated zona pellucida (ZP) components.

Design: Prospective study.

Setting: Basic research laboratory.

Patient(s): Recombinant proteins derived from human proacrosin (Rec-40, Rec-30, Rec-20, Rec-10, and Rec-6) and from human ZP glycoproteins (rec-hZPA, ZPB, and ZPC).

Intervention(s): In vitro binding assay developed to assess proacrosin/acrosin-ZP interaction.

Main outcome measure(s): Zona pellucida glycoprotein binding to proacrosin/acrosin; estimation of binding affinity.

Result(s): Of all ZP proteins, rec-hZPA demonstrated the highest binding activity toward acrosin (Rec-30) (rec-hZPB: 42% of rec-hZPA; rec-hZPC: 39% of rec-hZPA; P<.0005). Rec-hZPA interaction was disturbed by dextran sulphate (75% inhibition with 10 microM), fucose (67% inhibition with 1.5 microM), and mannose (69% inhibition with 333 mM). Comparing binding activity of proacrosin with other N-terminal acrosin fragments, Rec-40 showed 2.6-3 times higher levels. Moreover, saturable high affinity binding of Rec-40 to ZP components was observed (Kd: 34 nM for rec-hZPA, 38 nM for rec-hZPB, 63 nM for rec-hZPC).

Conclusion(s): The rec-hZPA is the major ZP ligand for human proacrosin/acrosin. The interaction involves mannosyl, fucosyl, and sulfated glycans. Binding sites for rec-hZP would be located both at the N- and C-terminus of proacrosin, revealing a key role of the proenzyme in the interaction.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrosin / chemistry
  • Acrosin / metabolism*
  • Acrosin / physiology
  • Animals
  • Binding Sites / physiology
  • CHO Cells
  • Cricetinae
  • Egg Proteins / metabolism*
  • Enzyme Precursors / chemistry
  • Enzyme Precursors / metabolism*
  • Enzyme Precursors / physiology
  • Humans
  • Male
  • Membrane Glycoproteins / metabolism*
  • Prospective Studies
  • Protein Binding / physiology
  • Receptors, Cell Surface / metabolism*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Zona Pellucida / enzymology*
  • Zona Pellucida / metabolism
  • Zona Pellucida / physiology
  • Zona Pellucida Glycoproteins

Substances

  • Egg Proteins
  • Enzyme Precursors
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • Recombinant Proteins
  • ZP4 protein, human
  • Zona Pellucida Glycoproteins
  • proacrosin
  • Acrosin