The UNC-45 molecular chaperone: Its interactions with myosin and its thermosensing properties

dc.contributor.advisorChoi, Kay
dc.contributor.committeeMemberOberhauser, Andres
dc.contributor.committeeMemberBarral, Jose
dc.contributor.committeeMemberMorais, Marc
dc.contributor.committeeMemberMarszalek, Piotr
dc.contributor.committeeMemberTaglialatela, Giulio
dc.creatorBujalowski, Pawel 2015
dc.description.abstractIn order to perform their biological functions, proteins must fold into a defined structure which is termed the “native state”. In some cases proteins can acquire the native structure spontaneously; however for others additional assistance of molecular chaperones is needed. The molecular chaperones are proteins which through interactions with the client proteins, prevent the formation of aggregates and promote the folding process without being present in their final structure. One of the most biologically significant proteins which require assistance of chaperones are myosins. These are motor proteins responsible together with actin for muscle contraction process. The UNC-45 protein is a chaperone that has been identified to be involved during the myosin folding process. During my thesis research, I have addressed the energetics of interactions of the UNC-45 chaperone and its domains with myosin. My results indicate that the myosin motor domain possesses two binding sites, which engage two different domains of the UNC-45 chaperone, namely the UCS and the Central domain. Interactions between the domains in the complex affect the UNC-45 chaperone affinity for myosin. Moreover, the experiments showed that the UCS domain alone is responsible for chaperone-like activity of UNC-45. I have also discovered that the chaperone-like UCS domain possesses thermosensing properties. I have found that the UCS domain undergoes significant structural rearrangements within the physiological temperature ranges of 38-41°C when the hydrophobic protein surfaces that were once deeply buried inside of protein core become accessible to solvent. These changes are results of alterations within the tertiary but not the secondary protein structure. Most importantly, the temperature which triggers the chaperone conformational changes is also the temperature of the myosin aggregation. Therefore, the results suggest that the UCS domain significant structural flexibility is required for the chaperone function.
dc.subjectChaperones, Myosin
dc.titleThe UNC-45 molecular chaperone: Its interactions with myosin and its thermosensing properties
dc.type.materialtext and Molecular Biology and Molecular Biology University of Texas Medical Branch at Galveston and Molecular Biology (Doctoral)


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