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Evolutionary, structural and functional interplay of the I?B family members.


ABSTRACT: A primary level of control for nuclear factor kappa B (NF-?B) is effected through its interactions with the inhibitor protein, inhibitor of kappa B (I?B). Several lines of evidence confirm the existence of multiple forms of I?B that appear to regulate NF-?B by distinct mechanisms. Therefore, we performed a comprehensive bioinformatics analysis to understand the evolutionary history and intrinsic functional diversity of I?B family members. Phylogenetic relationships were constructed to trace the evolution of the I?B family genes. Our phylogenetic analysis revealed 10 I?B subfamily members that clustered into 5 major clades. Since the ankyrin (ANK) domain appears to be more ancient than the Rel homology domain (RHD), our phylogenetic analysis suggests that some undefined ancestral set of ANK repeats acquired an RHD before any duplication and was later duplicated and then diverged into the different I?B subfamilies. Functional analysis identified several functionally divergent sites in the ANK repeat domains (ARDs) and revealed that this region has undergone strong purifying selection, suggesting its functional importance in I?B genes. Structural analysis showed that the major variations in the number of ANK repeats and high conformational changes in the finger loop ARD region contribute to the differing binding partner specificities, thereby leading to distinct I?B functions. In summary, our study has provided useful information about the phylogeny and structural and functional divergence of the I?B family. Additionally, we identified a number of amino acid sites that contribute to the predicted functional divergence of these proteins.

SUBMITTER: Basith S 

PROVIDER: S-EPMC3553144 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Evolutionary, structural and functional interplay of the IκB family members.

Basith Shaherin S   Manavalan Balachandran B   Gosu Vijayakumar V   Choi Sangdun S  

PloS one 20130123 1


A primary level of control for nuclear factor kappa B (NF-κB) is effected through its interactions with the inhibitor protein, inhibitor of kappa B (IκB). Several lines of evidence confirm the existence of multiple forms of IκB that appear to regulate NF-κB by distinct mechanisms. Therefore, we performed a comprehensive bioinformatics analysis to understand the evolutionary history and intrinsic functional diversity of IκB family members. Phylogenetic relationships were constructed to trace the  ...[more]

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