N-terminal Tail of Annexin A2: A Switch into Intrinsic Disorder

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N-terminal Tail of Annexin A2: A Switch into Intrinsic Disorder

Published Date

2015

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Scholarly Text or Essay

Abstract

Dysferlinopathies (e.g. Limb Girdle muscular dystrophy, Myoshi Myopathy) are muscle wasting diseases that develop from reduced levels or absence of the protein dysferlin. Dysferlin is known to be the Ca2+ sensor in membrane repair, a process involving a number of proteins, one of which is annexin A2 (A2). The interaction between these two proteins is unclear, but previous studies have shown dysferlin to be marginally stable. Because of this, we proposed that A2 is marginally stable as well in order to maximize the information flow between the two proteins. Specifically, we hypothesized that the N-terminal tail of annexin A2, a region unique to each annexin isoform, acts as a switch into intrinsic disorder where this N-termini destabilizes the core of the protein to allow more potential conformations of the protein. This would enable A2 to respond more acutely to signals from dysferlin as its binding partner. Using calorimetry and spectroscopy, we showed the presence of this disorder region generates a protein with greater plasticity (compared to a protein in the absence of this disordered region), creating a means by which dysferlin and annexin A2 can coordinate in membrane repair and shedding light on how mutations in either protein can lead to miscommunication, and potentially, disease.

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University Honors Capstone Project Paper, University of Minnesota Duluth, 2015. Department of Chemistry and Biochemistry.

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Schramel, Justine. (2015). N-terminal Tail of Annexin A2: A Switch into Intrinsic Disorder. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/199810.

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