Is There an Interplay Between the Functional Domains of IRAP?
As a member of the M1 family of aminopeptidases, insulin regulated aminopeptidase (IRAP) is characterized by distinct binding motifs at the active site in the C-terminal domain that mediate the catalysis of peptide substrates. However, what makes IRAP unique in this family of enzymes is that it also...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-09-01
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| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2020.585237/full |
| _version_ | 1819012237884391424 |
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| author | Anika Vear Tracey Gaspari Philip Thompson Siew Yeen Chai |
| author_facet | Anika Vear Tracey Gaspari Philip Thompson Siew Yeen Chai |
| author_sort | Anika Vear |
| collection | DOAJ |
| description | As a member of the M1 family of aminopeptidases, insulin regulated aminopeptidase (IRAP) is characterized by distinct binding motifs at the active site in the C-terminal domain that mediate the catalysis of peptide substrates. However, what makes IRAP unique in this family of enzymes is that it also possesses trafficking motifs at the N-terminal domain which regulate the movement of IRAP within different intracellular compartments. Research on the role of IRAP has focused predominantly on the C-terminus catalytic domain in different physiological and pathophysiological states ranging from pregnancy to memory loss. Many of these studies have utilized IRAP inhibitors, that bind competitively to the active site of IRAP, to explore the functional significance of its catalytic activity. However, it is unknown whether these inhibitors are able to access intracellular sites where IRAP is predominantly located in a basal state as the enzyme may need to be at the cell surface for the inhibitors to mediate their effects. This property of IRAP has often been overlooked. Interestingly, in some pathophysiological states, the distribution of IRAP is altered. This, together with the fact that IRAP possesses trafficking motifs, suggest the localization of IRAP may play an important role in defining its physiological or pathological functions and provide insights into the interplay between the two functional domains of the protein. |
| first_indexed | 2024-12-21T01:40:52Z |
| format | Article |
| id | doaj.art-2ea2031e37894859aa5ff554b87b8308 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-21T01:40:52Z |
| publishDate | 2020-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-2ea2031e37894859aa5ff554b87b83082022-12-21T19:20:09ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-09-01810.3389/fcell.2020.585237585237Is There an Interplay Between the Functional Domains of IRAP?Anika Vear0Tracey Gaspari1Philip Thompson2Siew Yeen Chai3Department of Physiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, AustraliaDepartment of Pharmacology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, AustraliaDepartment of Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, AustraliaDepartment of Physiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, AustraliaAs a member of the M1 family of aminopeptidases, insulin regulated aminopeptidase (IRAP) is characterized by distinct binding motifs at the active site in the C-terminal domain that mediate the catalysis of peptide substrates. However, what makes IRAP unique in this family of enzymes is that it also possesses trafficking motifs at the N-terminal domain which regulate the movement of IRAP within different intracellular compartments. Research on the role of IRAP has focused predominantly on the C-terminus catalytic domain in different physiological and pathophysiological states ranging from pregnancy to memory loss. Many of these studies have utilized IRAP inhibitors, that bind competitively to the active site of IRAP, to explore the functional significance of its catalytic activity. However, it is unknown whether these inhibitors are able to access intracellular sites where IRAP is predominantly located in a basal state as the enzyme may need to be at the cell surface for the inhibitors to mediate their effects. This property of IRAP has often been overlooked. Interestingly, in some pathophysiological states, the distribution of IRAP is altered. This, together with the fact that IRAP possesses trafficking motifs, suggest the localization of IRAP may play an important role in defining its physiological or pathological functions and provide insights into the interplay between the two functional domains of the protein.https://www.frontiersin.org/article/10.3389/fcell.2020.585237/fullIRAPAngiotensin IVM1 aminopeptidasepathophysiologytraffickingIRAP inhibitors |
| spellingShingle | Anika Vear Tracey Gaspari Philip Thompson Siew Yeen Chai Is There an Interplay Between the Functional Domains of IRAP? Frontiers in Cell and Developmental Biology IRAP Angiotensin IV M1 aminopeptidase pathophysiology trafficking IRAP inhibitors |
| title | Is There an Interplay Between the Functional Domains of IRAP? |
| title_full | Is There an Interplay Between the Functional Domains of IRAP? |
| title_fullStr | Is There an Interplay Between the Functional Domains of IRAP? |
| title_full_unstemmed | Is There an Interplay Between the Functional Domains of IRAP? |
| title_short | Is There an Interplay Between the Functional Domains of IRAP? |
| title_sort | is there an interplay between the functional domains of irap |
| topic | IRAP Angiotensin IV M1 aminopeptidase pathophysiology trafficking IRAP inhibitors |
| url | https://www.frontiersin.org/article/10.3389/fcell.2020.585237/full |
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