Human Epididymis Protein-4 (HE-4): A Novel Cross-Class Protease Inhibitor |
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| Authors: | Nirmal Chhikara Mayank Saraswat Anil Kumar Tomar Sharmistha Dey Sarman Singh Savita Yadav |
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| Institution: | 1. Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India.; 2. Department of Lab Medicine, All India Institute of Medical Sciences, New Delhi, India.; New York University, United States of America, |
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| Abstract: | Epididymal proteins represent the factors necessary for maturation of sperm and play a crucial role in sperm maturation. HE-4, an epididymal protein, is a member of whey acidic protein four-disulfide core (WFDC) family with no known function. A WFDC protein has a conserved WFDC domain of 50 amino acids with eight conserved cystine residue. HE-4 is a 124 amino acid long polypeptide with two WFDC domains. Here, we show that HE-4 is secreted in the human seminal fluid as a disulfide-bonded homo-trimer and is a cross-class protease inhibitor inhibits some of the serine, aspartyl and cysteine proteases tested using hemoglobin as a substrate. Using SPR we have also observed that HE-4 shows a significant binding with all these proteases. Disulfide linkages are essential for this activity. Moreover, HE-4 is N-glycosylated and highly stable on a wide range of pH and temperature. Taken together this suggests that HE-4 is a cross-class protease inhibitor which might confer protection against microbial virulence factors of proteolytic nature. |
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