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Deep Mutational Scanning of EccD3 Reveals the Molecular Basis of Its Essentiality in the Mycobacterium ESX Secretion System
Deep Mutational Scanning of EccD3 Reveals the Molecular Basis of Its Essentiality in the Mycobacterium ESX Secretion System
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211152717
- ISBN
- 9798384077596
- DDC
- 574
- 서명/저자
- Deep Mutational Scanning of EccD3 Reveals the Molecular Basis of Its Essentiality in the Mycobacterium ESX Secretion System
- 발행사항
- [Sl] : University of California, San Francisco, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 48 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-03, Section: B.
- 주기사항
- Advisor: Ernst, Joel.
- 학위논문주기
- Thesis (Ph.D.)--University of California, San Francisco, 2024.
- 초록/해제
- 요약Tuberculosis remains the deadliest infectious disease in the world and requires novel therapeutic targets. The ESX-3 secretion system, which is essential for iron and zinc homeostasis and thus M. tuberculosis survival, is a promising target. In this study, we perform a deep mutational scan on the ESX-3 core protein EccD3 in the model organism M. smegmatis. We systematically investigated the functional roles of 145 residues across the soluble ubiquitin-like domain, the conformationally distinct flexible linker, and selected transmembrane helices of EccD3. Our data combined with structural comparisons to ESX-5 complexes support a model where EccD3 stabilizes the complex, with the hinge motif within the linker being particularly sensitive to disruption. Our study is the first deep mutational scan in mycobacteria, which could help guide drug development toward novel treatment of tuberculosis. This study underscores the importance of context-specific mutational analyses for discovering essential protein interactions within mycobacterial systems.
- 일반주제명
- Molecular biology
- 일반주제명
- Microbiology
- 일반주제명
- Biochemistry
- 키워드
- M. smegmatis
- 키워드
- Tuberculosis
- 기타저자
- University of California, San Francisco Biomedical Sciences
- 기본자료저록
- Dissertations Abstracts International. 86-03B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■020 ▼a9798384077596
■035 ▼a(MiAaPQ)AAI31489162
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574
■1001 ▼aTrinidad, Donovan.▼0(orcid)0000-0002-1439-9927
■24510▼aDeep Mutational Scanning of EccD3 Reveals the Molecular Basis of Its Essentiality in the Mycobacterium ESX Secretion System
■260 ▼a[Sl]▼bUniversity of California, San Francisco▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a48 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-03, Section: B.
■500 ▼aAdvisor: Ernst, Joel.
■5021 ▼aThesis (Ph.D.)--University of California, San Francisco, 2024.
■520 ▼aTuberculosis remains the deadliest infectious disease in the world and requires novel therapeutic targets. The ESX-3 secretion system, which is essential for iron and zinc homeostasis and thus M. tuberculosis survival, is a promising target. In this study, we perform a deep mutational scan on the ESX-3 core protein EccD3 in the model organism M. smegmatis. We systematically investigated the functional roles of 145 residues across the soluble ubiquitin-like domain, the conformationally distinct flexible linker, and selected transmembrane helices of EccD3. Our data combined with structural comparisons to ESX-5 complexes support a model where EccD3 stabilizes the complex, with the hinge motif within the linker being particularly sensitive to disruption. Our study is the first deep mutational scan in mycobacteria, which could help guide drug development toward novel treatment of tuberculosis. This study underscores the importance of context-specific mutational analyses for discovering essential protein interactions within mycobacterial systems.
■590 ▼aSchool code: 0034.
■650 4▼aMolecular biology
■650 4▼aMicrobiology
■650 4▼aBiochemistry
■653 ▼aDeep mutational scanning
■653 ▼aM. smegmatis
■653 ▼aNext-generation sequencing
■653 ▼aTuberculosis
■653 ▼aProtein family secretion
■690 ▼a0307
■690 ▼a0410
■690 ▼a0487
■71020▼aUniversity of California, San Francisco▼bBiomedical Sciences.
■7730 ▼tDissertations Abstracts International▼g86-03B.
■790 ▼a0034
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17163505▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
