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On the segregation of protein ionic residues by charge type

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Abstract

Based on ubiquitous presence of large ionic motifs and clusters in proteins involved in gene transcription and protein synthesis, we analyzed the distribution of ionizable sidechains in a broad selection of proteins with regulatory, metabolic, structural and adhesive functions, in agonist, antagonist, toxin and antimicrobial peptides, and in self-excising inteins and intron-derived proteins and sequence constructs. All tested groups, regardless of taxa or sequence size, show considerable segregation of ionizable sidechains into same type charge (homoionic) tracts. These segments in most cases exceed half of the sequence length and comprise more than two-thirds of all ionizable sidechains. This distribution of ionic residues apparently reflects a fundamental advantage of sorted electrostatic contacts in association of sequence elements within and between polypeptides, as well as in interaction with polynucleotides. While large ionic densities are encountered in highly interactive proteins, the average ionic density in most sets does not change appreciably with size of the homoionic segments, which supports the segregation as a modular feature favoring association.

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Abbreviations

aa:

Amino acid (residue)

ec1:

First extracellular domain

GPCR:

G-protein coupling receptor

ic3:

Third intracellular domain

ic4:

Fourth intracellular domain

NLM:

US National Library of Medicine

u-p:

UniProtein database

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Acknowledgments

This work was partly supported by the U.S. National Institutes of Health grants R01-HD13703 and R01 HD-20074, and also in part by grants from Shriners Hospital for Children, #8570 and #86400 and a Department of Veteran Affairs Grant, 1I01BX000263 (to A.B.).

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The authors declare no conflicts of interest related to subjects of this study.

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Parker, M.S., Balasubramaniam, A. & Parker, S.L. On the segregation of protein ionic residues by charge type. Amino Acids 43, 2231–2247 (2012). https://doi.org/10.1007/s00726-012-1418-4

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