β防御素
中文名称
通路描述
人类有38个β防御素基因加上9-10个假基因（详情可参见HGNC网站）。许多β防御素由最近重复的基因编码，产生相同的转录本。命名目前混乱且处于过渡期。本通路使用UniProt推荐的名字。许多β防御素与感染相关表达（Sahl et al. 2005, Pazgier et al. 2006）。迄今为止已鉴定的所有β防御素（β防御素1(hBD1)、4A(hBD2)、103(hBD3)、104(hBD4)、106(hBD6)、118(hBD18)和128(hBD28)）都具有抗菌特性（Pazgier et al. 2006）。对于β防御素4A、103和118(hBD2、3和18)，这已被证明与膜通透性效应相关（Antcheva et al. 2004, Sahl et al. 2005, Yenugu et al. 2004）。静电相互作用和微生物膜破坏被认为是β防御素作用的主要机制。膜破坏有两种模型解释：'孔模型'，该模型假设β防御素以类似α防御素的方式形成跨膜孔；以及'地毯模型'，该模型认为β防御素作为洗涤剂发挥作用。β防御素含有6个保守的半胱氨酸残基，在β防御素1、4A和103(hBD1-3)中，实验证实它们以1-5、2-4、3-6的形式交联。β防御素的典型序列为x2-10Cx5-6(G/A)xCX3-4Cx9-13Cx4-7CCxn。结构上它们类似于α防御素，但预区域短得多。虽然某些β防御素的二聚化已被报道，但这并非所有β防御素的情况，且不清楚这是否是功能所必需的。功能研究主要集中在β防御素103(hBD3)上，它在生理盐浓度下具有最显著的抗菌活性（Harder et al. 2001）。β防御素103高度带正电，净电荷为+11 e0。它对革兰氏阳性菌和某些革兰氏阴性菌具有广谱抗菌活性（Harder et al. 2001），尽管某些物种具有高度耐药性（Sahly et al. 2003）。敏感性取决于膜脂质组成，与膜电容变化相关的是更带负电荷的脂质（Bohling et al. 2006）。虽然膜破坏被认为是β防御素的主要作用机制，但它们还具有其他抗菌特性，如细胞壁生物合成抑制（Sass et al. 2010）和趋化作用（Yang et al. 1999, Niyonsaba et al. 2002, 2004）。β防御素1、4A和103(hBD1-3)对记忆T细胞和 immature DCs的趋化作用是通过结合趋化因子受体CCR6和另一个未鉴定的Gi耦合受体介导的（Yang et al. 1999, 2000）。与防御素类似，人类cathelicidin LL37肽富含带正电荷的残基（Lehrer & Ganz 2002）。某些β防御素表达可受细菌、病原体相关分子模式(PAMPs)或促炎细胞因子等信号诱导（Ganz 2003, Yang et al. 2004）。与α防御素一样，DEFB4、DEFB103和DEFB104的拷贝数变异已被报道，个体每对二倍体基因组中有2-12个拷贝。相比之下，DEFB1不显示此类变异，但表现出许多SNPs（Hollox et al. 2003, Linzmier & Ganz 2005）。
英文描述
Respiratory syncytial virus genome transcription The negative sense, single-stranded RNA (-ssRNA) genome of the respiratory syncytial virus (RSV) is transcribed into 10 positive sense messenger RNAs that encode 11 viral proteins. The 10 viral mRNAs, going from the 3' end, are: 1C (NS1) mRNA,1B (NS2) mRNA, N mRNA, P mRNA, M mRNA, SH mRNA, G mRNA, F mRNA, M2 mRNA, and L mRNA. Except for the M2 mRNA, each mRNA contains a single open reading frame (ORF). The two overlapping open reading frames (ORFs) of the M2 mRNA are translated into two distinct proteins, M2-1 and M2-2.
The N mRNA encodes the nucleoprotein, while the L and P mRNAs encode the large polymerase subunit and the phosphoprotein polymerase cofactor subunit, respectively, of the RNA-dependent RNA polymerase complex (RdRP). The M2-1 mRNA encodes a transcription processivity factor, while the M2-2 mRNA encodes a nonstructural protein that regulates the switch between transcription and genome replication. The SH, G and F mRNAs encode three proteins that are embedded in the viral envelope: small hydrophobic protein, attachment protein and fusion protein, respectively. The secreted isoform of G protein (sG), involved in mediation of immune evasion, and the truncated form of SH (SHt), are translated from G mRNA and SH mRNA, respectively, through the usage of an alternative start codon. The NS1 and NS2 mRNAs encode nonstructural proteins that function together to inhibit apoptosis and interferon response in infected cells. All RSV mRNAs undergo 5' capping and 3' polyadenylation, performed by the viral RdRP. For review, please refer to Battles and McLellan 2019.
The N mRNA encodes the nucleoprotein, while the L and P mRNAs encode the large polymerase subunit and the phosphoprotein polymerase cofactor subunit, respectively, of the RNA-dependent RNA polymerase complex (RdRP). The M2-1 mRNA encodes a transcription processivity factor, while the M2-2 mRNA encodes a nonstructural protein that regulates the switch between transcription and genome replication. The SH, G and F mRNAs encode three proteins that are embedded in the viral envelope: small hydrophobic protein, attachment protein and fusion protein, respectively. The secreted isoform of G protein (sG), involved in mediation of immune evasion, and the truncated form of SH (SHt), are translated from G mRNA and SH mRNA, respectively, through the usage of an alternative start codon. The NS1 and NS2 mRNAs encode nonstructural proteins that function together to inhibit apoptosis and interferon response in infected cells. All RSV mRNAs undergo 5' capping and 3' polyadenylation, performed by the viral RdRP. For review, please refer to Battles and McLellan 2019.
所含基因
1 个基因