Conservation of the C-type lectin fold for accommodating massive sequence variation in archaeal diversity-generating retroelements.
Conservation of the C-type lectin fold for accommodating massive sequence variation in archaeal diversity-generating retroelements.
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DOI：
10.1186/s12900-016-0064-6
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发表时间：
2016-08-31
影响因子：
--
通讯作者：
Ghosh P
中科院分区：
文献类型：
--
作者：
Handa S;Paul BG;Miller JF;Valentine DL;Ghosh P
多样性生成逆转录元件(DGRs)通过大量的蛋白质序列变异为生物体提供了一种独特的适应动态环境的手段。这种变异的潜在范围超过了脊椎动物的适应性免疫系统。人们知道DGRs只存在于病毒和细菌中，直到最近在古生菌中发现了属于“微生物暗物质”的DGRs，特别是在与纳米考古群密切相关的生物体中。然而，纳米考古塔DGR可变蛋白不能分配到已知的蛋白质折叠中，而且显然与特定的DGR可变蛋白无关。为了解决纳米考古菌DGR可变蛋白如何适应大规模序列变异的问题，我们确定了其中一种蛋白质AVPA的2.52°分辨率极限晶体结构，它揭示了一个C型凝集素(CLEC)折叠，它组织了一个假定的配体结合位点，能够容纳1013个序列。这一折叠令人惊讶地想起病毒和细菌DGR可变蛋白的CLEC-折叠，但差异足以定义一个新的CLEC-折叠亚类，这与细菌和古生菌DGR之间的早期分歧一致。该结构还使从未培养的古菌中识别出多个可能的DGR中的一组AVPA样蛋白成为可能。这些可变的蛋白质可能有助于纳米考古菌和这些未培养的古菌建立共生关系。我们的结果揭示了CLEC-折叠在病毒、细菌和古菌中的广泛保守，以适应大规模的序列变异。此外，据我们所知，这是首次报道古生菌的CLEC-折叠蛋白。
Diversity-generating retroelements (DGRs) provide organisms with a unique means for adaptation to a dynamic environment through massive protein sequence variation. The potential scope of this variation exceeds that of the vertebrate adaptive immune system. DGRs were known to exist only in viruses and bacteria until their recent discovery in archaea belonging to the ‘microbial dark matter’, specifically in organisms closely related to Nanoarchaeota. However, Nanoarchaeota DGR variable proteins were unassignable to known protein folds and apparently unrelated to characterized DGR variable proteins. To address the issue of how Nanoarchaeota DGR variable proteins accommodate massive sequence variation, we determined the 2.52 Å resolution limit crystal structure of one such protein, AvpA, which revealed a C-type lectin (CLec)-fold that organizes a putative ligand-binding site that is capable of accommodating 1013 sequences. This fold is surprisingly reminiscent of the CLec-folds of viral and bacterial DGR variable protein, but differs sufficiently to define a new CLec-fold subclass, which is consistent with early divergence between bacterial and archaeal DGRs. The structure also enabled identification of a group of AvpA-like proteins in multiple putative DGRs from uncultivated archaea. These variable proteins may aid Nanoarchaeota and these uncultivated archaea in symbiotic relationships. Our results have uncovered the widespread conservation of the CLec-fold in viruses, bacteria, and archaea for accommodating massive sequence variation. In addition, to our knowledge, this is the first report of an archaeal CLec-fold protein.
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影响因子：
14.8
作者：
Kelley LA;Mezulis S;Yates CM;Wass MN;Sternberg MJ
通讯作者：
Sternberg MJ
DOI：
10.1107/s0907444905036693
发表时间：
2006-01-01
影响因子：
2.2
作者：
Evans, P
通讯作者：
Evans, P
DOI：
10.1107/s0907444910045749
发表时间：
2011-04
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Winn MD;Ballard CC;Cowtan KD;Dodson EJ;Emsley P;Evans PR;Keegan RM;Krissinel EB;Leslie AG;McCoy A;McNicholas SJ;Murshudov GN;Pannu NS;Potterton EA;Powell HR;Read RJ;Vagin A;Wilson KS
通讯作者：
Wilson KS
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
DOI：
10.1107/s0907444999000839
发表时间：
1999-04
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Terwilliger TC;Berendzen J
通讯作者：
Berendzen J