림프구항원96
Lymphocyte antigen 96| LY96 | |||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
 | |||||||||||||||||||||||||
| |||||||||||||||||||||||||
| 식별자 | |||||||||||||||||||||||||
| 에일리어스 | LY96, ESOP-1, MD-2, MD2, Ly-96, 림프구 항원 96 | ||||||||||||||||||||||||
| 외부 ID | OMIM: 605243 MGI: 1341909 HomoloGene: 9109 GeneCard: LY96 | ||||||||||||||||||||||||
| |||||||||||||||||||||||||
| |||||||||||||||||||||||||
| |||||||||||||||||||||||||
| 맞춤법 | |||||||||||||||||||||||||
| 종. | 인간 | 마우스 | |||||||||||||||||||||||
| 엔트레즈 | |||||||||||||||||||||||||
| 앙상블 | |||||||||||||||||||||||||
| 유니프로트 | |||||||||||||||||||||||||
| RefSeq(mRNA) | |||||||||||||||||||||||||
| RefSeq(단백질) | |||||||||||||||||||||||||
| 장소(UCSC) | Chr 8: 73.99 ~74.03 Mb | Chr 1: 16.76 ~16.78 Mb | |||||||||||||||||||||||
| PubMed 검색 | [3] | [4] | |||||||||||||||||||||||
| 위키데이터 | |||||||||||||||||||||||||
| |||||||||||||||||||||||||
"골수 분화 인자 2 (MD-2)"라고도 알려진 림프구 항원 96은 LY96 [5][6][7][8]유전자에 의해 인간에게 암호화되는 단백질이다.
이 유전자에 의해 암호화된 단백질은 Toll-Like Receptor(TLR4)와 리포다당류를 결합하는 데 관여한다.
기능.
MD-2 단백질은 세포 표면의 톨 유사 수용체 4와 관련지어 리포다당류(LPS)에 대한 반응성을 부여하여 수용체와 LPS [7]시그널링 사이의 연결을 제공한다.즉, TLR4와 MD-2 사이의 프라이머리 인터페이스는 LPS의 바인딩 전에 형성되어 LPS의 [8]바인딩에 의해 디머라이제이션인터페이스가 유도됩니다.
구조.
MD-2는 리간드 [9][10]결합용 큰 소수성 포켓을 형성하는 2장의 반평행 β 시트로 이루어진 β컵 폴드 구조를 가진다.
상호 작용
림프구 항원 96은 TLR [5][11]4와 상호작용하는 것으로 나타났다.
LPS가 MD-2의 소수성 포켓에 결합하면 2개의 TLR4-MD-2 복합체의 이량화를 직접 매개합니다.따라서 MD-2는 구조적으로 다양한 LPS 분자의 공통 패턴을 인식하는 헤테로디머를 형성한다.이러한 상호 작용을 통해 TLR4는 LPS를 [8]인식할 수 있습니다.MD-2 녹아웃 마우스의 대식세포는 LPS에 [12]반응하지 않는다.
LPS는 세균막에서 추출되어 LPS 결합단백질과 CD14의 2가지 부가단백질에 의해 TLR4-MD-2로 이행되어 선천적인 면역반응을 [8]유도한다.
레퍼런스
- ^ a b c GRCh38: 앙상블 릴리즈 89: ENSG00000154589 - 앙상블, 2017년 5월
- ^ a b c GRCm38: 앙상블 릴리즈 89: ENSMUSG000025779 - 앙상블, 2017년 5월
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b Shimazu R, Akashi S, Ogata H, Nagai Y, Fukudome K, Miyake K, Kimoto M (June 1999). "MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4". The Journal of Experimental Medicine. 189 (11): 1777–82. doi:10.1084/jem.189.11.1777. PMC 2193086. PMID 10359581.
- ^ Abreu MT, Vora P, Faure E, Thomas LS, Arnold ET, Arditi M (August 2001). "Decreased expression of Toll-like receptor-4 and MD-2 correlates with intestinal epithelial cell protection against dysregulated proinflammatory gene expression in response to bacterial lipopolysaccharide". Journal of Immunology. 167 (3): 1609–16. doi:10.4049/jimmunol.167.3.1609. PMID 11466383.
- ^ a b "Entrez Gene: LY96 lymphocyte antigen 96".
- ^ a b c d Park BS, Song DH, Kim HM, Choi BS, Lee H, Lee JO (April 2009). "The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex". Nature. 458 (7242): 1191–5. doi:10.1038/nature07830. PMID 19252480. S2CID 4396446.
- ^ Kim HM, Park BS, Kim JI, Kim SE, Lee J, Oh SC, et al. (September 2007). "Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran". Cell. 130 (5): 906–17. doi:10.1016/j.cell.2007.08.002. PMID 17803912. S2CID 18948568.
- ^ Ohto U, Fukase K, Miyake K, Satow Y (June 2007). "Crystal structures of human MD-2 and its complex with antiendotoxic lipid IVa". Science. 316 (5831): 1632–4. doi:10.1126/science.1139111. PMID 17569869. S2CID 37539892.
- ^ Re F, Strominger JL (June 2002). "Monomeric recombinant MD-2 binds toll-like receptor 4 tightly and confers lipopolysaccharide responsiveness". The Journal of Biological Chemistry. 277 (26): 23427–32. doi:10.1074/jbc.M202554200. PMID 11976338.
- ^ Ciesielska A, Matyjek M, Kwiatkowska K (2021). "TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling". Cellular and Molecular Life Sciences. 78 (4): 1233–1261. doi:10.1007/s00018-020-03656-y. PMC 7904555. PMID 33057840.
추가 정보
- Kato K, Morrison AM, Nakano T, Tashiro K, Honjo T (July 2000). "ESOP-1, a secreted protein expressed in the hematopoietic, nervous, and reproductive systems of embryonic and adult mice". Blood. 96 (1): 362–4. doi:10.1182/blood.V96.1.362. PMID 10891475.
- Dziarski R, Wang Q, Miyake K, Kirschning CJ, Gupta D (February 2001). "MD-2 enables Toll-like receptor 2 (TLR2)-mediated responses to lipopolysaccharide and enhances TLR2-mediated responses to Gram-positive and Gram-negative bacteria and their cell wall components". Journal of Immunology. 166 (3): 1938–44. doi:10.4049/jimmunol.166.3.1938. PMID 11160242.
- Schromm AB, Lien E, Henneke P, Chow JC, Yoshimura A, Heine H, Latz E, Monks BG, Schwartz DA, Miyake K, Golenbock DT (July 2001). "Molecular genetic analysis of an endotoxin nonresponder mutant cell line: a point mutation in a conserved region of MD-2 abolishes endotoxin-induced signaling". The Journal of Experimental Medicine. 194 (1): 79–88. doi:10.1084/jem.194.1.79. PMC 2193443. PMID 11435474.
- Visintin A, Mazzoni A, Spitzer JA, Segal DM (October 2001). "Secreted MD-2 is a large polymeric protein that efficiently confers lipopolysaccharide sensitivity to Toll-like receptor 4". Proceedings of the National Academy of Sciences of the United States of America. 98 (21): 12156–61. doi:10.1073/pnas.211445098. PMC 59784. PMID 11593030.
- Akashi S, Nagai Y, Ogata H, Oikawa M, Fukase K, Kusumoto S, Kawasaki K, Nishijima M, Hayashi S, Kimoto M, Miyake K (December 2001). "Human MD-2 confers on mouse Toll-like receptor 4 species-specific lipopolysaccharide recognition". International Immunology. 13 (12): 1595–9. doi:10.1093/intimm/13.12.1595. PMID 11717200.
- Abreu MT, Arnold ET, Thomas LS, Gonsky R, Zhou Y, Hu B, Arditi M (June 2002). "TLR4 and MD-2 expression is regulated by immune-mediated signals in human intestinal epithelial cells". The Journal of Biological Chemistry. 277 (23): 20431–7. doi:10.1074/jbc.M110333200. PMID 11923281.
- Re F, Strominger JL (June 2002). "Monomeric recombinant MD-2 binds toll-like receptor 4 tightly and confers lipopolysaccharide responsiveness". The Journal of Biological Chemistry. 277 (26): 23427–32. doi:10.1074/jbc.M202554200. PMID 11976338.
- Latz E, Visintin A, Lien E, Fitzgerald KA, Monks BG, Kurt-Jones EA, Golenbock DT, Espevik T (December 2002). "Lipopolysaccharide rapidly traffics to and from the Golgi apparatus with the toll-like receptor 4-MD-2-CD14 complex in a process that is distinct from the initiation of signal transduction". The Journal of Biological Chemistry. 277 (49): 47834–43. doi:10.1074/jbc.M207873200. PMID 12324469.
- Schröder NW, Morath S, Alexander C, Hamann L, Hartung T, Zähringer U, Göbel UB, Weber JR, Schumann RR (May 2003). "Lipoteichoic acid (LTA) of Streptococcus pneumoniae and Staphylococcus aureus activates immune cells via Toll-like receptor (TLR)-2, lipopolysaccharide-binding protein (LBP), and CD14, whereas TLR-4 and MD-2 are not involved". The Journal of Biological Chemistry. 278 (18): 15587–94. doi:10.1074/jbc.M212829200. PMID 12594207.
- Mullen GE, Kennedy MN, Visintin A, Mazzoni A, Leifer CA, Davies DR, Segal DM (April 2003). "The role of disulfide bonds in the assembly and function of MD-2". Proceedings of the National Academy of Sciences of the United States of America. 100 (7): 3919–24. doi:10.1073/pnas.0630495100. PMC 153023. PMID 12642668.
- Ohnishi T, Muroi M, Tanamoto K (May 2003). "MD-2 is necessary for the toll-like receptor 4 protein to undergo glycosylation essential for its translocation to the cell surface". Clinical and Diagnostic Laboratory Immunology. 10 (3): 405–10. doi:10.1128/cdli.10.3.405-410.2003. PMC 154975. PMID 12738639.
- Thompson PA, Tobias PS, Viriyakosol S, Kirkland TN, Kitchens RL (August 2003). "Lipopolysaccharide (LPS)-binding protein inhibits responses to cell-bound LPS". The Journal of Biological Chemistry. 278 (31): 28367–71. doi:10.1074/jbc.M302921200. PMID 12754215.
- Visintin A, Latz E, Monks BG, Espevik T, Golenbock DT (November 2003). "Lysines 128 and 132 enable lipopolysaccharide binding to MD-2, leading to Toll-like receptor-4 aggregation and signal transduction". The Journal of Biological Chemistry. 278 (48): 48313–20. doi:10.1074/jbc.M306802200. PMID 12960171.
- Re F, Strominger JL (November 2003). "Separate functional domains of human MD-2 mediate Toll-like receptor 4-binding and lipopolysaccharide responsiveness". Journal of Immunology. 171 (10): 5272–6. doi:10.4049/jimmunol.171.10.5272. PMID 14607928.
- Hamann L, Kumpf O, Müller M, Visintin A, Eckert J, Schlag PM, Schumann RR (June 2004). "A coding mutation within the first exon of the human MD-2 gene results in decreased lipopolysaccharide-induced signaling". Genes and Immunity. 5 (4): 283–8. doi:10.1038/sj.gene.6364068. PMID 15057266.
- Gruber A, Mancek M, Wagner H, Kirschning CJ, Jerala R (July 2004). "Structural model of MD-2 and functional role of its basic amino acid clusters involved in cellular lipopolysaccharide recognition". The Journal of Biological Chemistry. 279 (27): 28475–82. doi:10.1074/jbc.M400993200. PMID 15111623.
- Cario E, Golenbock DT, Visintin A, Rünzi M, Gerken G, Podolsky DK (April 2006). "Trypsin-sensitive modulation of intestinal epithelial MD-2 as mechanism of lipopolysaccharide tolerance". Journal of Immunology. 176 (7): 4258–66. doi:10.4049/jimmunol.176.7.4258. PMID 16547263.
- Jia HP, Kline JN, Penisten A, Apicella MA, Gioannini TL, Weiss J, McCray PB (August 2004). "Endotoxin responsiveness of human airway epithelia is limited by low expression of MD-2". American Journal of Physiology. Lung Cellular and Molecular Physiology. 287 (2): L428-37. doi:10.1152/ajplung.00377.2003. PMID 15121639. S2CID 13203884.
외부 링크
- 림프구+항원+96, 미국 국립의학도서관 의학 과목 표제(MeSH)의 인간
