N-Terminal myristoylation alters the calcium binding pathways in neuronal calcium sensor-1

Chandra, Kousik ; Ramakrishnan, Venkatesh ; Sharma, Yogendra ; Chary, K. V. R. (2011) N-Terminal myristoylation alters the calcium binding pathways in neuronal calcium sensor-1 Journal of Biological Inorganic Chemistry, 16 (1). pp. 81-95. ISSN 0949-8257

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Official URL: http://www.springerlink.com/content/l643x1h471406t...

Related URL: http://dx.doi.org/10.1007/s00775-010-0705-3

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.

Item Type:Article
Source:Copyright of this article belongs to Springer.
Keywords:Neuronal Calcium Sensor-1; Spectral Density; Parallel/Sequential Filling; EFβ-scaffold Model; Monod; Wyman; Changeux Model
ID Code:50896
Deposited On:27 Jul 2011 13:29
Last Modified:18 May 2016 05:02

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