Abstract
The human retroviral-like aspartic protease 1 (ASPRV1) is a mammalian retroviral-like enzyme that catalyzes a critical proteolytic step during epidermal differentiation; therefore, it is also referred to as skin-specific aspartic protease (SASPase). Neutrophil granulocytes were also found recently to express ASPRV1 that is involved in the progression of acute chronic inflammation of the central nervous system, especially in autoimmune encephalomyelitis. Thus, investigation of ASPRV1 is important due to its therapeutic or diagnostic potential. We investigated the structural characteristics of ASPRV1 by homology modeling; analysis of the proposed structure was used for interpretation of in vitro specificity studies. For in-vitro characterization, activities of SASP28 and SASP14 enzyme forms were measured using synthetic oligopeptide substrates. We demonstrated that self-processing of SASP28 precursor causes autoactivation of the protease. The highest activity was measured for GST-SASP14 at neutral pH and at high ionic strength, and we proved that pepstatin A and acetyl-pepstatin can also inhibit the protease. In agreement with the structural characteristics, the relatively lower urea dissociation constant implied lower dimer stability of SASP14 compared to that of HIV-1 protease. The obtained structural and biochemical characteristics support better understanding of ASPRV1 function in the skin and central nervous system.
Highlights
IntroductionThe retroviral-like aspartic protease 1 (ASPRV1) is an endogenously expressed mammalian protein
The retroviral-like aspartic protease 1 (ASPRV1) is an endogenously expressed mammalian protein. It has been identified as a protease of the human epidermis (EC: 3.4.23.-) that is expressed in the granular layer of the skin, it is referred to as skin-specific aspartic protease (SASPase) [1,2]
Prediction implied that the homodimeric SASP14 has a six-stranded dimer interface, because the C-terminal region was predicted to contain three β-strands connected by short loops (Figure 1)
Summary
The retroviral-like aspartic protease 1 (ASPRV1) is an endogenously expressed mammalian protein. It has been identified as a protease of the human epidermis (EC: 3.4.23.-) that is expressed in the granular layer of the skin, it is referred to as skin-specific aspartic protease (SASPase) [1,2]. Keratinocytes show characteristic morphological and biochemical changes while migrating toward upper layers. During their terminal differentiation and particular form of apoptosis, the keratinocytes lose their intracellular organelles and transform into flattened dead cells (corneocytes), which are eliminated from the skin surface by desquamation [3]. The differentiating keratinocytes express several proteases (PR), which are organized into cascades; the activation of these proteolytic cascades is essential for the maintenance of skin physiology due to proteolytic processing of target proteins [4]
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