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The Structural Basis for Allosteric Regulation of Protein Assembly in Cancer Progression and Circadian Rhythms
The Structural Basis for Allosteric Regulation of Protein Assembly in Cancer Progression and Circadian Rhythms
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211152046
- ISBN
- 9798384049586
- DDC
- 574.191
- 저자명
- Feng, Shi.
- 서명/저자
- The Structural Basis for Allosteric Regulation of Protein Assembly in Cancer Progression and Circadian Rhythms
- 발행사항
- [Sl] : Cornell University, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 227 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-03, Section: B.
- 주기사항
- Advisor: Cerione, Richard.
- 학위논문주기
- Thesis (Ph.D.)--Cornell University, 2024.
- 초록/해제
- 요약Proteins function as molecular machines, facilitating various cellular activities. In the dynamic cellular environment, proteins interact with binding partners to catalyze reactions, transduce signals, or serve as scaffolds. Over the past two decades, advances in structural biology have expanded the tools available for protein structure determination, enabling visualization of ever more complex states at the molecular level. Cryogenic electron microscopy (Cryo-EM) has emerged as a powerful technique, providing high-resolution structures for proteins that are otherwise challenging to study, such as those with disordered regions and post-translational modifications or that function through oligomerization. During my Ph.D. research in the Cerione and Crane labs, I utilized Cryo-EM and other biophysical methods to investigate proteins involved in cancer and circadian rhythms. My research focused on elucidating the mechanisms by which these proteins function through allosteric conformational changes. In the Cerione lab, I studied glutaminase, a key metabolic enzyme implicated in cancer progression and considered a potential drug target. My findings revealed that glutaminase activity is coupled to filament formation, with two flexible regions: the activation loop and lid loop, forming a substrate lock that optimally positions the substrate for enzymatic activity. In the Crane lab, I investigated circadian clock proteins that regulate universal rhythms in animals, plants, and fungi. I resolved the first structure of a cryptochrome photoreceptor bound to its target, which elucidated regulation of the downstream circadian clock repressor Timeless. Additionally, I deciphered how a post-translationally modified and disordered region of Timeless regulates its nuclear entry. Overall my work reveals how coupled conformational changes in protein complexes propagate to regulate enzymatic activity and signal transduction.
- 일반주제명
- Biophysics
- 일반주제명
- Biochemistry
- 일반주제명
- Cellular biology
- 일반주제명
- Oncology
- 키워드
- Circadian clock
- 키워드
- Enzyme
- 키워드
- Protein
- 기타저자
- Cornell University Biophysics
- 기본자료저록
- Dissertations Abstracts International. 86-03B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■006m o d
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■020 ▼a9798384049586
■035 ▼a(MiAaPQ)AAI31337374
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574.191
■1001 ▼aFeng, Shi.▼0(orcid)0000-0001-9084-3957
■24510▼aThe Structural Basis for Allosteric Regulation of Protein Assembly in Cancer Progression and Circadian Rhythms
■260 ▼a[Sl]▼bCornell University▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a227 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-03, Section: B.
■500 ▼aAdvisor: Cerione, Richard.
■5021 ▼aThesis (Ph.D.)--Cornell University, 2024.
■520 ▼aProteins function as molecular machines, facilitating various cellular activities. In the dynamic cellular environment, proteins interact with binding partners to catalyze reactions, transduce signals, or serve as scaffolds. Over the past two decades, advances in structural biology have expanded the tools available for protein structure determination, enabling visualization of ever more complex states at the molecular level. Cryogenic electron microscopy (Cryo-EM) has emerged as a powerful technique, providing high-resolution structures for proteins that are otherwise challenging to study, such as those with disordered regions and post-translational modifications or that function through oligomerization. During my Ph.D. research in the Cerione and Crane labs, I utilized Cryo-EM and other biophysical methods to investigate proteins involved in cancer and circadian rhythms. My research focused on elucidating the mechanisms by which these proteins function through allosteric conformational changes. In the Cerione lab, I studied glutaminase, a key metabolic enzyme implicated in cancer progression and considered a potential drug target. My findings revealed that glutaminase activity is coupled to filament formation, with two flexible regions: the activation loop and lid loop, forming a substrate lock that optimally positions the substrate for enzymatic activity. In the Crane lab, I investigated circadian clock proteins that regulate universal rhythms in animals, plants, and fungi. I resolved the first structure of a cryptochrome photoreceptor bound to its target, which elucidated regulation of the downstream circadian clock repressor Timeless. Additionally, I deciphered how a post-translationally modified and disordered region of Timeless regulates its nuclear entry. Overall my work reveals how coupled conformational changes in protein complexes propagate to regulate enzymatic activity and signal transduction.
■590 ▼aSchool code: 0058.
■650 4▼aBiophysics
■650 4▼aBiochemistry
■650 4▼aCellular biology
■650 4▼aOncology
■653 ▼aCancer metabolism
■653 ▼aCircadian clock
■653 ▼aCryogenic electron microscopy
■653 ▼aEnzyme
■653 ▼aProtein
■653 ▼aStructural biology
■690 ▼a0786
■690 ▼a0487
■690 ▼a0379
■690 ▼a0992
■71020▼aCornell University▼bBiophysics.
■7730 ▼tDissertations Abstracts International▼g86-03B.
■790 ▼a0058
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17162720▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
