Sandhya Sankaran, Rani Saane Sudha, Pankaj Barah, Govind Madabosse Kande, Offmann Bernard, Srinivasan Narayanaswamy, Sowdhamini Ramanathan
National Centre for Biological Sciences (TIFR), GKVK Campus, Bangalore, India.
PLoS One. 2009;4(3):e4981. doi: 10.1371/journal.pone.0004981. Epub 2009 Mar 31.
Related protein domains of a superfamily can be specified by proteins of diverse lengths. The structural and functional implications of indels in a domain scaffold have been examined.
In this study, domain superfamilies with large length variations (more than 30% difference from average domain size, referred as 'length-deviant' superfamilies and 'length-rigid' domain superfamilies (<10% length difference from average domain size) were analyzed for the functional impact of such structural differences. Our delineated dataset, derived from an objective algorithm, enables us to address indel roles in the presence of peculiar structural repeats, functional variation, protein-protein interactions and to examine 'domain contexts' of proteins tolerant to large length variations. Amongst the top-10 length-deviant superfamilies analyzed, we found that 80% of length-deviant superfamilies possess distant internal structural repeats and nearly half of them acquired diverse biological functions. In general, length-deviant superfamilies have higher chance, than length-rigid superfamilies, to be engaged in internal structural repeats. We also found that approximately 40% of length-deviant domains exist as multi-domain proteins involving interactions with domains from the same or other superfamilies. Indels, in diverse domain superfamilies, were found to participate in the accretion of structural and functional features amongst related domains. With specific examples, we discuss how indels are involved directly or indirectly in the generation of oligomerization interfaces, introduction of substrate specificity, regulation of protein function and stability.
Our data suggests a multitude of roles for indels that are specialized for domain members of different domain superfamilies. These specialist roles that we observe and trends in the extent of length variation could influence decision making in modeling of new superfamily members. Likewise, the observed limits of length variation, specific for each domain superfamily would be particularly relevant in the choice of alignment length search filters commonly applied in protein sequence analysis.
一个超家族的相关蛋白质结构域可由不同长度的蛋白质来确定。已对结构域支架中插入缺失的结构和功能影响进行了研究。
在本研究中，分析了具有较大长度差异的结构域超家族（与平均结构域大小相差超过30%，称为“长度偏差”超家族）和“长度刚性”结构域超家族（与平均结构域大小相差<10%），以探讨此类结构差异的功能影响。我们通过一种客观算法划定的数据集，使我们能够在存在特殊结构重复、功能变异、蛋白质-蛋白质相互作用的情况下研究插入缺失的作用，并研究耐受大长度变异的蛋白质的“结构域背景”。在分析的前10个长度偏差超家族中，我们发现80%的长度偏差超家族具有远距离内部结构重复，其中近一半获得了多种生物学功能。一般来说，长度偏差超家族比长度刚性超家族更有可能参与内部结构重复。我们还发现，约40%的长度偏差结构域以多结构域蛋白质的形式存在，涉及与来自相同或其他超家族的结构域相互作用。在不同的结构域超家族中，插入缺失被发现参与相关结构域之间结构和功能特征的积累。通过具体例子，我们讨论了插入缺失如何直接或间接参与寡聚化界面的产生、底物特异性的引入、蛋白质功能和稳定性的调节。
我们的数据表明插入缺失对不同结构域超家族的结构域成员具有多种作用。我们观察到的这些特殊作用以及长度变异程度的趋势可能会影响新超家族成员建模的决策。同样，每个结构域超家族特有的观察到的长度变异限度在蛋白质序列分析中常用的比对长度搜索过滤器的选择中尤为重要。
