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Structural Modeling of Human Akap3 Protein and in Silico Analysis of Single Nucleotide Polymorphisms Associated With Sperm Motility Publisher Pubmed



Rafaee A1, 2 ; Kashaniamin E3 ; Meybodi AM4, 5 ; Ebrahimhabibi A3 ; Sabbaghian M1
Authors
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Authors Affiliations
  1. 1. Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
  2. 2. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
  3. 3. Biosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
  5. 5. Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada

Source: Scientific Reports Published:2022


Abstract

AKAP3 is a member of the A-kinase anchoring proteins and it is a constituent of the sperm fibrous sheath. AKAP3 is needed for the formation of sperm flagellum structure, sperm motility, and male fertility. This study aims to model the AKAP3 tertiary structure and identify the probable impact of four mutations characterized in infertile men on the AKAP3 structure. The T464S, I500T, E525K, and I661T substitutions were analyzed using in silico methods. The secondary structure and three-dimensional model of AKAP3 were determined using PSI-BLAST based secondary structure prediction and Robetta servers. The TM-score was used to quantitatively measure the structural similarities between native and mutated models. All of the desired substitutions were classified as benign. I-Mutant results showed all of the substitutions decreased AKAP3 stability; however, the I500T and I661T were more effective. Superposition and secondary structure comparisons between native and mutants showed no dramatic deviations. Our study provided an appropriate model for AKAP3. Destabilization of AKAP3 caused by these substitutions did not appear to induce structural disturbances. As AKAP3 is involved in male infertility, providing more structural insights and the impact of mutations that cause protein functional diversity could elucidate the etiology of male fertility problems at molecular level. © 2022, The Author(s).
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