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Chemical Proteomic Mapping of Heme-Protein Interactions Utilizing Photoaffinity Probes
Chemical Proteomic Mapping of Heme-Protein Interactions Utilizing Photoaffinity Probes
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211151937
- ISBN
- 9798383567654
- DDC
- 574
- 저자명
- Homan, Rick A.
- 서명/저자
- Chemical Proteomic Mapping of Heme-Protein Interactions Utilizing Photoaffinity Probes
- 발행사항
- [Sl] : The Scripps Research Institute, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 271 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-01, Section: B.
- 주기사항
- Includes supplementary digital materials.
- 주기사항
- Advisor: Parker, Christopher G.
- 학위논문주기
- Thesis (Ph.D.)--The Scripps Research Institute, 2024.
- 초록/해제
- 요약Heme is a ubiquitously expressed small molecule modulator of protein function that participates in enzymatic reactions as a prosthetic group and acts as a signaling molecule to coordinate several facets of metabolism. Upon cellular damage, unbound "free" heme is released from cells and the heme binding proteins they contain, leading to oxidative damage of cellular components and activating inflammatory signals, serving as a damage-associated molecular pattern. In this context, free heme plays a pivotal role in pathological mechanisms of sterile and pathogenic hemolytic conditions, such as malaria, hemolytic anemias, and injury causing hemorrhage. Heme has been speculated to stimulate immune cells such as leukocytes through activation of precise signaling pathways via direct binding to innate immune receptors. However, the mechanisms by which heme causes the activation of pro-inflammatory responses is not fully understood. This is due to a lack of available tools to study transient heme-protein interactions in native systems. Here, we describe a strategy which utilizes a heme-based photoaffinity probe integrated with chemical proteomic methods to map heme-protein interactions across the proteome. We aim to elucidate specific proteins and biochemical pathways involved in the regulation of heme-dependent signaling functions in immune cells and ascertain the functional consequences and roles of identified immunomodulatory proteins in heme-induced signaling; we highlight examples such as CD36, a heme binding protein identified herein and annotated multifunctional scavenger receptor involved in pattern recognition and activation of immune cells and IRAK1, a pro-inflammatory signaling kinase which serves as a critical signaling node in toll-like receptor-mediated pattern recognition and inflammation.
- 일반주제명
- Biochemistry
- 일반주제명
- Cellular biology
- 일반주제명
- Immunology
- 키워드
- Immune cells
- 기타저자
- The Scripps Research Institute Chemical Biology
- 기본자료저록
- Dissertations Abstracts International. 86-01B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■006m o d
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■020 ▼a9798383567654
■035 ▼a(MiAaPQ)AAI31301703
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574
■1001 ▼aHoman, Rick A.
■24510▼aChemical Proteomic Mapping of Heme-Protein Interactions Utilizing Photoaffinity Probes
■260 ▼a[Sl]▼bThe Scripps Research Institute▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a271 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-01, Section: B.
■500 ▼aIncludes supplementary digital materials.
■500 ▼aAdvisor: Parker, Christopher G.
■5021 ▼aThesis (Ph.D.)--The Scripps Research Institute, 2024.
■520 ▼aHeme is a ubiquitously expressed small molecule modulator of protein function that participates in enzymatic reactions as a prosthetic group and acts as a signaling molecule to coordinate several facets of metabolism. Upon cellular damage, unbound "free" heme is released from cells and the heme binding proteins they contain, leading to oxidative damage of cellular components and activating inflammatory signals, serving as a damage-associated molecular pattern. In this context, free heme plays a pivotal role in pathological mechanisms of sterile and pathogenic hemolytic conditions, such as malaria, hemolytic anemias, and injury causing hemorrhage. Heme has been speculated to stimulate immune cells such as leukocytes through activation of precise signaling pathways via direct binding to innate immune receptors. However, the mechanisms by which heme causes the activation of pro-inflammatory responses is not fully understood. This is due to a lack of available tools to study transient heme-protein interactions in native systems. Here, we describe a strategy which utilizes a heme-based photoaffinity probe integrated with chemical proteomic methods to map heme-protein interactions across the proteome. We aim to elucidate specific proteins and biochemical pathways involved in the regulation of heme-dependent signaling functions in immune cells and ascertain the functional consequences and roles of identified immunomodulatory proteins in heme-induced signaling; we highlight examples such as CD36, a heme binding protein identified herein and annotated multifunctional scavenger receptor involved in pattern recognition and activation of immune cells and IRAK1, a pro-inflammatory signaling kinase which serves as a critical signaling node in toll-like receptor-mediated pattern recognition and inflammation.
■590 ▼aSchool code: 1179.
■650 4▼aBiochemistry
■650 4▼aCellular biology
■650 4▼aImmunology
■653 ▼aEnzymatic reactions
■653 ▼aPathogenic hemolytic conditions
■653 ▼aImmune cells
■653 ▼aHemolytic anemias
■653 ▼aBiochemical pathways
■690 ▼a0487
■690 ▼a0379
■690 ▼a0982
■71020▼aThe Scripps Research Institute▼bChemical Biology.
■7730 ▼tDissertations Abstracts International▼g86-01B.
■790 ▼a1179
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17162143▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
