همایش ملی بیوانفورماتیک ایران

صفحه اصلی / 4th international edition and 13th Iranian Conference on Bioinformatics

Bioinformatics and computational Studies on Highly Conserved Neurocalcin Protein

نویسندگان :

Ali Eyvazi¹ Khosrow Khalifeh² Emran Heshmati³

1- دانشگاه زنجان 2- دانشگاه زنجان 3- دانشگاه زنجان

کلمات کلیدی :

Neurocalcin،bioinformatics analysis،EF-hand motif

چکیده :

Neuronal Calcium Sensors are a class of calcium-binding proteins that play important roles in various neural functions, including calcium signaling processes. Neurocalcin, a member of this protein family, contains 193 residues (Ivings et al., 2002). Its 3D structure has been determined for the Bos taurus (Bovine) variant. The aim of this study is to conduct a bioinformatics analysis on the sequence and structure of Neurocalcin to develop a biological model for its evolution. The protein sequence and its corresponding information were obtained from the UniProt database (ID: P61601). (Bateman et al., 2021). A similarity search using the local pairwise alignment algorithm implemented in the BLAST program (McWilliam et al., 2013) revealed that the protein is present in 250 different species, of which eight variants are experimentally reviewed proteins. Multiple sequence alignment of the reviewed sequences using the Clustal Omega program (Sievers et al., 2011) surprisingly showed that only two positions have been permitted to accept the random mutations during the evolutionary timescale. The high conservation of the sequence among different organisms suggests that it has been evolutionarily optimized to recognize various targets, limiting its ability to tolerate sequence changes. In other words, any change in the sequence could be deleterious for the organism due to the loss of its ability to interact with some targets. This hypothesis is consistent with the current activity data, which indicates that the protein functions through interactions with other neural system proteins. Dot Plot analysis revealed that Neurocalcin contains four repeating regions, which are the calcium-binding EF-hand motifs.(Burgoyne, 2007) Structurally, it has been reported that among the four calcium-binding loops, only loops II, III, and IV are capable of coordinating calcium ions, while loop I has lost its calcium-binding function. Our computational study suggests that the first loop, which is distinguished from the others by a unique Cys-Pro dipeptide, is involved in dimerization of the protein. We conclude that the dimeric form of the protein, containing six calcium ions and a larger surface area compared to the monomeric form, may be the functional unit. The increased surface area of the dimer could enable simultaneous interactions with two or more targets, allowing the protein to function more effectively. According to our model, the evolution of the Neurocalcin involve multitarget and simultaneous binding to various targets. The first one limits its tolerance against random mutations leading to high level of identity between its sequence in various organisms, and the second parameter needs more surface area which is obtained by dimerization of the protein due to losing calcium binding affinity at the first EF-hand loop.