N-terminal myristoylation alters the calcium binding pathways in neuronal calcium sensor-1 |
| |
Authors: | Kousik?Chandra,Venkatesh?Ramakrishnan,Yogendra?Sharma,K.?V.?R.?Chary author-information" > author-information__contact u-icon-before" > mailto:chary@tifr.res.in" title=" chary@tifr.res.in" itemprop=" email" data-track=" click" data-track-action=" Email author" data-track-label=" " >Email author |
| |
Affiliation: | (1) Department of Chemical Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai, 400005, India;(2) Centre for Cellular and Molecular Biology (CCMB), Uppal Road, Hyderabad, 500007, India; |
| |
Abstract: | Neuronal calcium sensor-1 (NCS-1) interacts with many membranes and cytosolic proteins, both in a Ca2+-dependent and in a Ca2+-independent manner, and its physiological role is governed by its N-terminal myristoylation. To understand the role of myristoylation in altering Ca2+ response and other basic biophysical properties, we have characterized the Ca2+ filling pathways in both myristoylated (myr) and non-myristoylated (non-myr) forms of NCS-1. We have observed that Ca2+ binds simultaneously to all three active EF-hands in non-myr NCS-1, whereas in the case of myr NCS-1, the process is sequential, where the second EF-hand is filled first, followed by the third and fourth EF-hands. In the case of myr NCS-1, the observed sequential Ca2+ binding process becomes more prominent in the presence of Mg2+. Besides, the analysis of 15N-relaxation data reveals that non-myr NCS-1 is more dynamic than myr NCS-1. The overall molecular tumbling correlation time increases by approximately 20% upon myristoylation. Comparing the apo forms of non-myr NCS-1 and myr NCS-1, we found the possibility of existence of some substates, which are structurally closer to the holo form of the protein. There are more such substates in the case of non-myr NCS-1 than in the case of the myr NCS-1, suggesting that the former accesses larger volumes of conformational substates compared with the latter. Further, the study reveals that the possibility of Ca2+ binding simultaneously to different parts of the protein is more favourable in non-myr NCS-1 than in myr NCS-1. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|