Related Experiment Video

Updated: May 26, 2026

Medium-throughput Screening Assays for Assessment of Effects on Ca2+-Signaling and Acrosome Reaction in Human Sperm
05:44

Medium-throughput Screening Assays for Assessment of Effects on Ca2+-Signaling and Acrosome Reaction in Human Sperm

Published on: March 1, 2019

Structure and inhibition of the sperm TMEM95-FIMP complex in mammalian fertilization

Pulan Liu1, Rithik E Castelino1, Taylor R Gierke1

  • 1Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA 06520.

Biorxiv : the Preprint Server for Biology
|May 25, 2026
PubMed

Insights

Researchers identified the TMEM95-FIMP protein complex, crucial for mammalian fertilization. This discovery reveals how TMEM95 facilitates sperm-egg interaction and membrane fusion, offering new insights into reproductive biology.

Area of Science:

  • Reproductive Biology
  • Molecular Biology
  • Structural Biology

Background:

  • TMEM95 is a vital sperm acrosomal membrane protein for mammalian fertilization.
  • The precise mechanism by which TMEM95 mediates sperm-egg interaction remains unclear.
  • Sperm fertilization proteins often function as complexes, suggesting TMEM95 may interact with other sperm proteins.

Purpose of the Study:

  • To identify TMEM95 binding partners on sperm.
  • To elucidate the structural basis of the TMEM95 interaction.
  • To investigate the functional significance of the TMEM95 interaction in fertilization.

Main Methods:

  • Utilized AlphaFold3 to predict protein interactions between TMEM95 and testis-expressed proteins.
  • Employed single-particle cryo-electron microscopy (cryo-EM) to determine the structure of the TMEM95-FIMP complex.
  • Generated and characterized an anti-TMEM95 antibody (3A02) to probe the TMEM95-FIMP interaction and its functional role.

Main Results:

  • Identified Fertilization-Essential Acrosomal Membrane Protein (FIMP) as a high-confidence binding partner of TMEM95.
  • Determined the high-resolution cryo-EM structure of the human TMEM95-FIMP ectodomain complex, revealing an ectodomain interaction mediated by a FIMP aromatic motif.
  • Showed that the anti-TMEM95 antibody 3A02 binds to the FIMP-binding site on TMEM95 and inhibits sperm-egg fusion, highlighting the critical role of the TMEM95-FIMP interface.

Conclusions:

  • Established the TMEM95-FIMP complex as a key player in human sperm function.
  • Demonstrated that the TMEM95-FIMP interaction is essential for membrane fusion during mammalian fertilization.
  • The findings suggest a FIMP-mediated mechanism for TMEM95 in facilitating fertilization.

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