Show simple item record

Structural biology of GroEL assisted protein folding

dc.contributor.advisorLorimer, George Hen_US
dc.contributor.authorFei, Xueen_US
dc.date.accessioned2015-02-06T06:38:02Z
dc.date.available2015-02-06T06:38:02Z
dc.date.issued2014en_US
dc.identifierhttps://doi.org/10.13016/M2X896
dc.identifier.urihttp://hdl.handle.net/1903/16169
dc.description.abstractGroEL/ES is the classical example of molecular chaperone that assists the re-folding of many misfolded proteins (SP). Recent kinetic analyses revealed a new paradigm of how GroEL/ES uses ATP to assist protein folding. Following these pioneering biochemical studies, I address two fundamental questions related to GroEL-assisted protein folding using structural biology methods. First, how does GroEL capture SP and how does SP change the kinetics of ADP release? Second, how does GroEL/ES encapsulate SP and control the duration of SP encapsulation? Chapter 1 summarizes the ATPase cycle of GroEL revealed by systematic biochemical studies, and identifies knowledge gaps in the GroEL-assisted protein folding. Chapter 2 describes general methods of protein purification and computational approaches, used to analyze conformational differences between two GroEL structures. Chapter 3 and 4 are focused on the capturing of substrate protein by GroEL. Crystal structures of GroELD83AR197A-ADP14 and GroELD83AR197A show for the first time, ADP binding breaks seven-fold symmetry in the apical and intermediate domains. Such asymmetry provides the structural basis for GroEL to capture heterogeneous SPs and for SP to regulate the release of ADP. In chapter 5, I described how GroEL/ES encapsulates substrate protein. Two crystal structures of the predominate SP encapsulation complexes: GroEL-GroES2 "football" complex were reported. One of the complexes is SP free and the other encapsulates two Rubisco molecules simultaneously. From the conformational rearrangement of the inter-ring interface, we proposed "football" complex transmits ATP asymmetry between the rings through an electrostatic interaction between K105 and A109. Chapter 6 summarized the new knowledge gained by determining these four crystal structures. This chapter ends with a discussion on how chaperonin machine like GroEL promotes the correct folding of various proteins.en_US
dc.language.isoenen_US
dc.titleStructural biology of GroEL assisted protein foldingen_US
dc.typeDissertationen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.contributor.departmentBiophysics (BIPH)en_US
dc.subject.pqcontrolledBiophysicsen_US
dc.subject.pqcontrolledBiochemistryen_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record