Part:BBa_K4990007

HlpA

Usage in short

You can use it to target coloretal cancer! Sequence and Features

Assembly Compatibility:

• 10
  COMPATIBLE WITH RFC[10]
• 12
  COMPATIBLE WITH RFC[12]
• 21
  COMPATIBLE WITH RFC[21]
• 23
  COMPATIBLE WITH RFC[23]
• 25
  INCOMPATIBLE WITH RFC[25]

  Illegal NgoMIV site found at 231
  
• 1000
  COMPATIBLE WITH RFC[1000]

What you need to know!

2006年Tjalsma通过Highly accurate tandem MS方法，找到了一种蛋白Histone-like protein A(HlpA),发现它联系Streptococcus bovis和结直肠癌的桥梁，并推测S.bovis正是通过HlpA与结直肠癌细胞表面的heparan sulfate-proteoglycans(HSPG)结合，介导的S.bovis定植于结直肠癌[1]。

2009年Boleij证明了Streptococcus gallolyticus通过HlpA于结直肠癌细胞表面的HSPG结合[2]。

2016年O'Neil得到了Hlp的晶体结构，指示Hlp为类似蟹钳的结构，钳子部分的碱性氨基酸可以与DNA结合，同时也可以与肝素结合[3]。

2018年Chun Loong Ho利用HlpA与HSPG的结合，构建了一种可以靶向结直肠癌的工程大肠杆菌，拉开了HlpA靶向系统的序幕[4]。

2022年iGEM22_LZU-CHINA 团队，通过合成生物学构建了靶向结直肠癌的大肠杆菌，方法为HlpA靶向肿瘤细胞表面的HSPG[5]。

2023年Tang构建了利用HlpA靶向，Azurin杀伤的工程益生菌，并在结直肠癌小鼠中展现出不错的疗效[6]。

Figure A:Crystal structure of HlpA(O'Neil 2016) Figure B:Engineered EcN treat CRC(Chun 2018)

HlpA(Histone-like protein A)正如其名，它能和组蛋白一样结合DNA。它整体形态如同一个蟹钳，能够利用其丝带般的β折叠区与DNA小沟非特异性紧密结合，which leads to significant DNA bending, DNA compaction and negative supercoiling。而S.boivs会通过一种未知的机制将其分泌出胞外，作为anchorless protein，是感染时体液免疫系统的靶标，通过连接细菌lipoteichoic acid(LTA)和结肠上皮细胞上的HSPG介导细菌粘附于结肠肿瘤细胞。

Therefore, HlpA possesses dual capabilities: 1. Targeting colorectal cancer and 2. Non-specifically binding to DNA chains.

What is it?

Here is the structure of HlpA monomer and homodimer.

Two helical segments from each monomeric subunit constitute an α-helical ‘body’ with two protruding β-ribbon ‘arms’ , which extend to bind the DNA helix. These DNA-binding β-ribbons are largely disordered in the absence of DNA

Two helical segments from each monomeric subunit constitute an α-helical ‘body’ with two protruding β-ribbon ‘arms’ , which extend to bind the DNA helix. These DNA-binding β-ribbons are largely disordered in the absence of DNA

Referrence

[1]Tjalsma H, Schöller‐Guinard M, Lasonder E, et al. Profiling the humoral immune response in colon cancer patients: diagnostic antigens from Streptococcus bovis[J]. International journal of cancer, 2006, 119(9): 2127-2135.

[2]Boleij A, Schaeps R M J, de Kleijn S, et al. Surface-exposed histone-like protein a modulates adherence of Streptococcus gallolyticus to colon adenocarcinoma cells[J]. Infection and immunity, 2009, 77(12): 5519-5527.

[3]O'Neil P, Lovell S, Mehzabeen N, et al. Crystal structure of histone-like protein from Streptococcus mutans refined to 1.9 Å resolution[J]. Acta Crystallographica Section F: Structural Biology Communications, 2016, 72(4): 257-262.

[4]Ho C L, Tan H Q, Chua K J, et al. Engineered commensal microbes for diet-mediated colorectal-cancer chemoprevention[J]. Nature biomedical engineering, 2018, 2(1): 27-37.

[5]https://2022.igem.wiki/lzu-china/

[6]