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Albany 2015:Book of Abstracts

Albany 2015
Conversation 19
June 9-13 2015
©Adenine Press (2012)

Influence of Homo-Repeats on Functions and Aggregation Propensities of Protein Chains

Single amino acid repeats or homo-repeats represent an unexplored area with many connections to genome function and evolution. What homo-repeat is expected to occur at a specific length in a proteome? In a large-scale analysis, we calculated amino acid frequencies for ∼1.5 millions of proteins measuring occurrences at various sequence lengths and in 122 eukaryotic and bacterial proteomes. We found that the number of proteins with homo-repeats is significantly larger than what expected from theoretical estimates (Fig.1). As long homo-repeats are present in proteins with a high number of interactions, we hypothesize that a strong positive selection acts in their evolution. Is there a link between diseases and occurrence of specific homo-repeats? Considering MIM database of human disease, we found that the homo-repeats with length larger than four for such amino acids as Leucine, Serine, Alanine, Glycine, and Proline have a larger propensity to be coupled with disease. Indeed, it has been found that developmental diseases are associated with homo-repeat expansions such as poly-A (alanine): synpolydactyly type II (HOXD13), blepharophimosis (FOXL2), oculopharyngeal muscular dystrophy (PABPN1), infantile spasm syndrome (ARX), and holoprosencephaly (ZIC2). Also, expansion of poly-Q is implicated in several neurodegenerative diseases, including Huntington's disease and several spinocerebellar ataxia's. The length of homo-repeats which can affect on aggregation properties has been found for each amino acid and compared with random proteomes. It has been found that the longer homo-repeats occur in a protein the stronger aggregation ability we observe for protein sequence. The ability to regulate aggregation of proteins can be one of the general tools for the drug development.

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Figure 1. Dependence of the number of proteins that contain homo-repeats of different lengths for 20 amino acids in Dictyostelium discoideum proteome.

This research has been supported by the Russian Science Foundation Grant 14-14-00536.

Oxana V. Galzitskaya
Mikhail Lobanov

Group of Bioinformatics of Institute of Protein Research
Pushchino
Moscow region, Russia, 142290

Ph: (+74967) 318275
Fx: (+74967) 418435
ogalzit@vega.protres.ru