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Fold combinations in multi-domain proteins


Nagarajan Naveenkumar1,2,3, Gayatri Kumar33, Ramanathan Sowdhamini1, Narayanaswamy Srinivasan*,3 & Sneha Vishwanath3



1National Center for Biological Science, GKVK Campus, Bengaluru, Karnataka, India 560065; 2Bharathidasan University, Tiruchirappalli, Tamil Nadu, 620024, India; 3Molecular Biophysics Unit, Indian Institute of Science, Bengaluru, Karnataka, India 560012



Narayanaswamy Srinivasan - E-mail:; *Corresponding author


Article Type

Research Article



Received May 5, 2019; Accepted May 7, 2019; Published May 15, 2019



Domain-domain interactions in multi-domain proteins with tethering domains play an important role in the combined function of individual domains for the overall biological activity of the protein. The functions of the tethered domains are often coupled and hence, limited numbers of domain architectures with defined folds (known 1439) are known in nature. Therefore, it is of interest to document the available fold-fold combinations and their preference in multi-domain proteins. Hence, we analyzed all multi-domain proteins with known structures at the protein databank (PDB) and observed that only about 860 fold-fold combinations are present among them. This represents about 29,860 fold-fold combinations in the known sequence space upon projection and it accounts for only 2.8% of all possible 1,036,080 (1439C2) fold-fold combinations in theory. The observed preference for fold-fold combinations in multi-domain proteins is interesting in the context of multiple functions through structural adaptation by gene fusion.



domain architecture; domain folds; multi-domain proteins; protein evolution; protein structure



Naveenkumar et al. Bioinformation 15(5): 342-350 (2019)


Edited by

P Kangueane






Biomedical Informatics



This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.