title: Human epididymis protein-4 (HE-4): a novel cross-class protease inhibitor.
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.
authors.affiliation: Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Nirmal
authors.initials: N
authors.lastname: Chhikara
authors.forename: Mayank
authors.initials: M
authors.lastname: Saraswat
authors.forename: Anil Kumar
authors.initials: AK
authors.lastname: Tomar
authors.forename: Sharmistha
authors.initials: S
authors.lastname: Dey
authors.forename: Sarman
authors.initials: S
authors.lastname: Singh
authors.forename: Savita
authors.initials: S
authors.lastname: Yadav
mesh_terms: D002846:Chromatography, Affinity; D002850:Chromatography, Gel; D002852:Chromatography, Ion Exchange; D002853:Chromatography, Liquid; D006031:Glycosylation; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D063347:Native Polyacrylamide Gel Electrophoresis; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011480:Protease Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization; D011506:Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D012661:Semen / Q000378:metabolism; D020539:Sequence Analysis, Protein; D020349:Surface Plasmon Resonance; D000081102:WAP Four-Disulfide Core Domain Protein 2
chemical_list: D010455:Peptides; D011480:Protease Inhibitors; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human