Structural disorder: a tool for housekeeping proteins performing tissue-specific interactions

Abstract

An interaction between a pair of proteins unique for a particular tissue is denoted as a tissue-specific interaction (TSI). Tissue-specific (TS) proteins always perform TSIs with a limited number of interacting partners. However, it has been claimed that housekeeping (HK) proteins frequently take part in TSIs. This is actually an unusual phenomenon. How a single HK protein mediates TSIs – remains an interesting yet an unsolved question. We have hypothesized that HK proteins have attained a high degree of structural flexibility to modulate TSIs efficiently. We have observed that HK proteins are selected to be intrinsically disordered compared to TS proteins. Therefore, the purposeful adaptation of structural disorder brings out special advantages for HK proteins compared to TS proteins. We have demonstrated that TSIs may play vital roles in shaping the molecular adaptation of disordered regions within HK proteins. We also have noticed that HK proteins, mediating a huge number of TSIs, have a greater portion of their interacting interfaces overlapped with the adjacent disordered segment. Moreover, these HK proteins, mediating TSIs, preferably adapt single domain (SD). We have concluded that HK proteins adapt a high degree of structural flexibility to mediate TSIs. Besides, having a SD along with structural flexibility is more economic than maintaining multiple domains with a rigid structure. This assists them in attaining various structural conformations upon binding to their partners, thereby designing an economically optimum molecular system.

Keywords:

• intrinsically disordered proteins
• unstructured proteins
• protein domains
• single domain proteins
• TSI index

Acknowledgments

We thank Bin Xue for predicting the protein disorder using the PONDR-FIT server. We also thank Lukasz Kurgan and Chen Wang for providing the web server that predicts molecular recognition elements within disordered regions. Above all, we are thankful to the anonymous reviewers and the editor for their valuable suggestions that have helped us to improve the quality of the manuscript.