抗菌肽

抗菌肽（Cathelicidin），係一系列可在巨噬細胞和中性粒細胞的溶酶體中找到的具有抗菌作用的多肽^[1]。這種多肽在哺乳動物對侵襲性細菌感染的先天免疫中扮演著重要的角色^[2]。抗菌肽家族被歸爲抗微生物肽（antimicrobial peptides ，縮寫爲AMPs）的一種。防禦素則是抗微生物肽家族的另一成員。儘管抗菌肽家族與防禦素具有相同的結構特徵，但它們卻具有高度異質性^[2]。

抗菌肽 Cathelicidin antimicrobial peptide
以蛋白質資料庫（PDB） 2FBS爲基礎的經渲染版本
有效結構 PDB 直系同源檢索：PDBe, RCSB PDB查詢代碼列表 2FBS, 2FBU, 2FCG, 2K6O, 2LMF, 4EYC
標識
代號	CAMP; CAP-18; CAP18; CRAMP; FALL-39; FALL39; HSD26; LL37
擴展標識	遺傳學：600474 鼠基因：108443 同源基因：110678 GeneCards: CAMP Gene
基因本體論描述 分子功能 · protein binding 細胞成分 · extracellular space · cell wall · cytosol · extracellular exosome 生物過程 · innate immune response in mucosa · antibacterial humoral response · defense response to bacterium · negative regulation of growth of symbiont on or near host surface · defense response to Gram-positive bacterium · interaction with host · killing by host of symbiont cells · phagosome maturation Sources: Amigo / QuickGO
RNA表達模式
更多表達數據
直系同源體
物種	人類	小鼠
Entrez	820	12796
Ensembl	ENSG00000164047	ENSMUSG00000038357
UniProt	P49913	P51437
mRNA序列	NM_004345	NM_009921
蛋白序列	NP_004336	NP_034051
基因位置	Chr 3: 48.22 – 48.23 Mb	Chr 9: 109.85 – 109.85 Mb
PubMed查詢	[1]	[2]
閱 論 編

注意：本條目介紹的不是「抗微生物肽」（Antimicrobial peptides）

抗菌肽家族的成員可通過一個高度穩定的區域（即凱薩林域（cathelin domain））和另一個高度可變的域來表徵^[2]。

哺乳動物的各個種的抗菌肽之間是互相孤立的。最初，科學家在中性粒細胞中發現了抗菌肽，不過，隨後，科學家發現，在經過細菌或病毒或骨化三醇（維生素D的活性形式）的刺激後，上皮細胞和巨噬細胞中亦會產生抗菌肽^[3]。

特徵

抗菌肽 Cathelicidin
內源性抗微生物多肽的抗菌肽基序（the Cathelicidin Motif of Protegrins）的晶體結構分析
鑑定
標誌	Cathelicidin
Pfam	PF00666（舊版）
Pfam宗系	CL0121（舊版）
InterPro（英語：InterPro）	IPR001894
PROSITE（英語：PROSITE）	PDOC00729
SCOP（英語：Structural Classification of Proteins）	1lyp / SUPFAM
OPM（英語：Orientations of Proteins in Membranes database）家族	236
OPM（英語：Orientations of Proteins in Membranes database）蛋白	2k6o
現有可用的蛋白結構： Pfam 結構（舊版） / ECOD PDB RCSB PDB; PDBe; PDBj PDBsum（英語：PDBsum） 結構概要

抗菌肽的長度範圍很大，其長度可從12個胺基酸殘基到80個胺基酸殘基。它們的結構也千變萬化^[4]。大部分的抗菌肽均爲摺疊成兩親性的α螺旋的長爲23-37個胺基酸的線狀肽。不過也有小部分的抗菌肽長度在12-18個胺基酸之間。這類肽有一到兩個起穩定結構作用的二硫鍵，且擁有β髮夾（英語：beta hairpin）結構。科學家也有發現長度較長的抗菌肽（長度在39-80個胺基酸殘基之間）。這些長度較長的抗菌肽呈現出重複的脯氨酸基序，形成了延長的聚脯氨酸型結構^[2]。

抗菌肽與半胱氨酸蛋白酶抑製劑（英語：Cystatin）家族有著一級同源性^[5]，儘管那些被認爲很重要的胺基酸殘基在這一蛋白酶抑制家族中往往難以找到。

種類

抗菌肽家族的成員在人類、猴子、小鼠、大鼠、豚鼠、熊貓、豬、牛、青蛙、綿羊、山羊、雞，還有馬體內都有分佈。

如今已被確認的抗菌肽有：^[2]

• 人類：hCAP-18/LL-37
• 恆河猴：RL-37
• 小鼠：CRAMP-1/2^[6]
• 大鼠：rCRAMP
• 兔：CAP-18
• 豚鼠：CAP-11
• 豬：PR-39、Prophenin、PMAP-23/6/37
• 牛：BMAP-27/28/34（牛髓細胞抗菌肽）、Bac5、Bac7
• 青蛙：抗菌肽-AL（在棕點湍蛙（Amolops loloensis）體內存在）^[7]

• 羊：
• 山羊：
• 雞：fowlicidins 1/2/3以及抗菌肽β-1（cathelicidin Beta-1）^[8]
• 馬：
• 熊貓：

臨床意義

患酒渣鼻的患者體內的抗菌肽水平和角質層胰蛋白酶酵素（SCTEs）水平會升高。在激肽釋放酶7（英語：KLK7）（KLK7）和激肽釋放酶5（英語：KLK5）（KLK5）的共同作用下，抗菌肽能被切割成抗微生物肽LL-37。LL-37過量被認爲是引發酒渣鼻（無論是其哪一亞種）的罪魁禍首之一^[9]。抗生素已被用於酒渣鼻的治療，然而，抗生素之所以起作用，或許僅僅是因爲它部分抑制了角質層胰蛋白酶酵素^[10]。

維生素D能提高的人體內抗菌肽hCAP18的水平，而hCAP18據信能有效降低接受透析的患者因感染而造成的死亡風險。擁有高水平hCAP18蛋白的患者經過一年透析之後能存活並免受致命感染的概率是一般患者的3.7倍。^[11]。

維生素D能夠增強抗菌肽相關基因的表達，而抗菌肽又對細菌，真菌和病毒具有廣譜抗微生物活性^[12][13]。抗菌肽能在巨噬細胞內的吞噬體與溶酶體融合後快速摧毀原來吞噬體裏的微生物的脂蛋白膜。

資料庫

針對抗菌胜肽，提供相關資訊的研究型資料庫，如: DRAMP^[14] [3] （頁面存檔備份，存於網際網路檔案館）, dbAMP [4] 。 dbAMP 為一個綜合型抗菌胜肽資料庫，其中所包含的資訊有抗菌胜肽蛋白質序列、名稱、物種來源、抗菌物種分類、抗菌胜肽的物理性質、是否經實驗研究證明以及蛋白質結構分析與圖形化等資訊，此些資料庫同時也提供抗菌胜肽等預測工具，供使用者瀏覽、分析及研究應用。

參見

• 抗微生物肽
• 先天免疫系統
• 理察·加洛（英語：Richard Gallo）

參考

1. Entrez Gene: CAMP cathelicidin antimicrobial peptide.
2. Zanetti M. Cathelicidins, multifunctional peptides of the innate immunity. Journal of Leukocyte Biology. Jan 2004, 75 (1): 39–48. PMID 12960280. doi:10.1189/jlb.0403147.
3. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, Ochoa MT, Schauber J, Wu K, Meinken C, Kamen DL, Wagner M, Bals R, Steinmeyer A, Zügel U, Gallo RL, Eisenberg D, Hewison M, Hollis BW, Adams JS, Bloom BR, Modlin RL. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science (New York, N.Y.). Mar 2006, 311 (5768): 1770–3. PMID 16497887. doi:10.1126/science.1123933.
4. Gennaro R, Zanetti M. Structural features and biological activities of the cathelicidin-derived antimicrobial peptides. Biopolymers. 2000, 55 (1): 31–49. PMID 10931440. doi:10.1002/1097-0282(2000)55:1<31::AID-BIP40>3.0.CO;2-9.
5. Zaiou M, Nizet V, Gallo RL. Antimicrobial and protease inhibitory functions of the human cathelicidin (hCAP18/LL-37) prosequence. The Journal of Investigative Dermatology. May 2003, 120 (5): 810–6. PMID 12713586. doi:10.1046/j.1523-1747.2003.12132.x3.
6. Gallo RL, Kim KJ, Bernfield M, Kozak CA, Zanetti M, Merluzzi L, Gennaro R. Identification of CRAMP, a cathelin-related antimicrobial peptide expressed in the embryonic and adult mouse. The Journal of Biological Chemistry. May 1997, 272 (20): 13088–93. PMID 9148921. doi:10.1074/jbc.272.20.13088.
7. Hao X, Yang H, Wei L, Yang S, Zhu W, Ma D, Yu H, Lai R. Amphibian cathelicidin fills the evolutionary gap of cathelicidin in vertebrate. Amino Acids. Aug 2012, 43 (2): 677–85. PMID 22009138. doi:10.1007/s00726-011-1116-7.
8. Achanta M, Sunkara LT, Dai G, Bommineni YR, Jiang W, Zhang G. Tissue expression and developmental regulation of chicken cathelicidin antimicrobial peptides. Journal of Animal Science and Biotechnology. 2012, 3 (1): 15. PMC 3436658 . PMID 22958518. doi:10.1186/2049-1891-3-15.
9. Reinholz M, Ruzicka T, Schauber J. Cathelicidin LL-37: an antimicrobial peptide with a role in inflammatory skin disease. Ann Dermatol. 2012, 24 (2): 126–35. PMC 3346901 . PMID 22577261. doi:10.5021/ad.2012.24.2.126.
10. Yamasaki K, Di Nardo A, Bardan A, Murakami M, Ohtake T, Coda A, Dorschner RA, Bonnart C, Descargues P, Hovnanian A, Morhenn VB, Gallo RL. Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nature Medicine. Aug 2007, 13 (8): 975–80. PMID 17676051. doi:10.1038/nm1616.
11. Gombart AF, Bhan I, Borregaard N, Tamez H, Camargo CA, Koeffler HP, Thadhani R. Low plasma level of cathelicidin antimicrobial peptide (hCAP18) predicts increased infectious disease mortality in patients undergoing hemodialysis. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. Feb 2009, 48 (4): 418–24. PMID 19133797. doi:10.1086/596314.
12. Zasloff M. Antimicrobial peptides of multicellular organisms. Nature. Jan 2002, 415 (6870): 389–95. PMID 11807545. doi:10.1038/415389a.
13. Kamen DL, Tangpricha V. Vitamin D and molecular actions on the immune system: modulation of innate and autoimmunity. Journal of Molecular Medicine (Berlin, Germany). May 2010, 88 (5): 441–50. PMC 2861286 . PMID 20119827. doi:10.1007/s00109-010-0590-9.
14. Shi, Guobang; Kang, Xinyue; Dong, Fanyi; Liu, Yanchao; Zhu, Ning; Hu, Yuxuan; Xu, Hanmei; Lao, Xingzhen; Zheng, Heng. DRAMP 3.0: an enhanced comprehensive data repository of antimicrobial peptides. Nucleic Acids Research. 2022-01-07, 50 (D1): D488–D496 [2022-04-25]. ISSN 0305-1048. PMC 8728287 . PMID 34390348. doi:10.1093/nar/gkab651. （原始內容存檔於2022-06-20） （英語）.

拓展閱讀

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• Gombart AF, Borregaard N, Koeffler HP. Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology. Jul 2005, 19 (9): 1067–77. PMID 15985530. doi:10.1096/fj.04-3284com.
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• Gudmundsson GH, Agerberth B, Odeberg J, Bergman T, Olsson B, Salcedo R. The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL-37 in granulocytes. European Journal of Biochemistry / FEBS. Jun 1996, 238 (2): 325–32. PMID 8681941. doi:10.1111/j.1432-1033.1996.0325z.x.
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• Frohm M, Agerberth B, Ahangari G, Stâhle-Bäckdahl M, Lidén S, Wigzell H, Gudmundsson GH. The expression of the gene coding for the antibacterial peptide LL-37 is induced in human keratinocytes during inflammatory disorders. The Journal of Biological Chemistry. Jun 1997, 272 (24): 15258–63. PMID 9182550. doi:10.1074/jbc.272.24.15258.
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