Related Experiment Video
Updated: May 13, 2026
Reconstitution of Msp1 Extraction Activity with Fully Purified Components
Published on: August 10, 2021
Mutational tail loss is an evolutionary mechanism for liberating marapsins and other type I serine proteases from
Kavita Raman1, Neil N Trivedi, Wilfred W Raymond
1Cardiovascular Research Institute, University of California, San Francisco, California 94143, USA.
Abstract:
Human and mouse marapsins (Prss27) are serine proteases preferentially expressed by stratified squamous epithelia. However, mouse marapsin contains a transmembrane anchor absent from the human enzyme. To gain insights into physical forms, activities, inhibition, and roles in epithelial differentiation, we traced tail loss in human marapsin to a nonsense mutation in an ancestral ape, compared substrate preferences of mouse and human marapsins with those of the epithelial peptidase prostasin, designed a selective substrate and inhibitor, and generated Prss27-null mice. Phylogenetic analysis predicts that most marapsins are transmembrane proteins. However, nonsense mutations caused membrane anchor loss in three clades: human/bonobo/chimpanzee, guinea pig/degu/tuco-tuco/mole rat, and cattle/yak. Most marapsin-related proteases, including prostasins, are type I transmembrane proteins, but the closest relatives (prosemins) are not. Soluble mouse and human marapsins are tryptic with subsite preferences distinct from those of prostasin, lack general proteinase activity, and unlike prostasins resist antiproteases, including leupeptin, aprotinin, serpins, and α2-macroglobulin, suggesting the presence of non-canonical active sites. Prss27-null mice develop normally in barrier conditions and are fertile without overt epithelial defects, indicating that marapsin does not play critical, non-redundant roles in development, reproduction, or epithelial differentiation. In conclusion, marapsins are conserved, inhibitor-resistant, tryptic peptidases. Although marapsins are type I transmembrane proteins in their typical form, they mutated independently into anchorless forms in several mammalian clades, including one involving humans. Similar pathways appear to have been traversed by prosemins and tryptases, suggesting that mutational tail loss is an important means of evolving new functions of tryptic serine proteases from transmembrane ancestors.
Insights
Marapsins (Prss27) are serine proteases. Though typically transmembrane, humans evolved an anchorless form, but Prss27-null mice show no developmental defects, indicating non-essential roles.
Area of Science:
- Biochemistry
- Evolutionary Biology
- Molecular Biology
Background:
- Marapsins (Prss27) are serine proteases found in stratified squamous epithelia.
- Mouse marapsin has a transmembrane anchor, unlike the human form.
Purpose of the Study:
- Investigate marapsin's physical forms, activities, inhibition, and role in epithelial differentiation.
- Trace the evolutionary loss of the transmembrane anchor in human marapsin.
- Determine the function of marapsin in vivo.
Main Methods:
- Phylogenetic analysis to predict protein structures.
- Comparative analysis of substrate preferences between human, mouse marapsins, and prostasin.
- Generation and study of Prss27-null mice.
- Design of selective substrates and inhibitors.
Main Results:
- Marapsins are typically transmembrane serine proteases, but anchorless forms evolved independently in several mammalian clades, including humans.
- Soluble human and mouse marapsins exhibit distinct tryptic activity and resistance to common antiproteases.
- Prss27-null mice exhibit normal development, fertility, and epithelial integrity.
Conclusions:
- Marapsins are conserved, inhibitor-resistant tryptic peptidases.
- Loss of the transmembrane anchor occurred independently in multiple lineages, suggesting evolutionary plasticity.
- Marapsin is not essential for normal development, reproduction, or epithelial differentiation in mice.
More Related Videos
05:56Exploring Caspase Mutations and Post-Translational Modification by Molecular Modeling Approaches
Published on: October 13, 2022
09:13Understanding the Development of Compensatory Pathways in a Mutant Malaria Parasite Harbouring Hypomorphic Allele of Plant-Like Kinases
Published on: November 22, 2024
Related Concept Videos
01:45Tail-anchoring of Proteins in the ER Membrane
01:19Translocation of Proteins into the Mitochondria
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
01:26Insertion of Single-pass Transmembrane Proteins in the RER
Integral transmembrane proteins possess transmembrane and extra membrane domains. The transmembrane domains are primarily made of 20-25 hydrophobic amino acids arranged in a helical secondary confirmation. These...
01:39Mitochondrial Precursor Proteins
Most of the mitochondrial precursors...
01:32Export of Misfolded Proteins out of the ER
02:10Translesion DNA Polymerases
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...