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Biological NMR Spectroscopy$
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John L. Markley and Stanley J. Opella

Print publication date: 1997

Print ISBN-13: 9780195094688

Published to Oxford Scholarship Online: November 2020

DOI: 10.1093/oso/9780195094688.001.0001

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Multidimensional NMR Investigation of the Neurotoxic Peptide Mastoparan in the Absence and Presence of Calmodulin

Multidimensional NMR Investigation of the Neurotoxic Peptide Mastoparan in the Absence and Presence of Calmodulin

(p.169) 13 Multidimensional NMR Investigation of the Neurotoxic Peptide Mastoparan in the Absence and Presence of Calmodulin
Biological NMR Spectroscopy

F. Mari

X. Xie

Oxford University Press

Calmodulin (CaM) is the major Ca2+ receptor in eukaryotic cells (Means and Rasmussen, 1988). This paper begins an investigation into the structural requirements for neurotoxic peptide binding to CaM. In resting cells, CaM is deficient in Ca2+ (the protein has the potential for binding four Ca2+ ions with high affinity, pKd > 6 (Means and Rasmussen, 1988)). Following nerve cell excitation, intracellular levels of Ca2+ increase dramatically, from about 0.1 μM to about 10 μM, allowing CaM to become fully-loaded with Ca2+ . Ca2+ - loaded CaM has the ability to activate a number of neural enzymes, including cyclic nucleotide phosphodiesterase, adenylate cyclase, Ca2+ - CaM kinase and calcineurin (Kennedy, 1989). A tight-binding neurotoxic peptide would be expected to competitively inhibit activation of these enzymes. The high level of intercellular coordination required by higher organisms is attained, in part, by the complex interplay of the nervous and endocrine systems. Two important second messengers are involved in information transfer processes associated with the normal operation of these two systems: cyclic AMP (cAMP) and Ca2+ . Cyclic AMP is involved in trans-membrane information flow following the interaction of cell surface receptors with certain hormones (e.g., glucagon, epinephrine and ACTH), while Ca2+ is the principal information carrier in the nerve cell following stimulation of the system by membrane depolarization. CaM plays a pivotal role in second messenger function in both the nervous and endocrine systems. In the nervous system, calmodulin is the principal target for Ca2+. In the endocrine system, CaM (complexed with Ca2+) is responsible for activating the enzymes responsible for both cAMP synthesis (i.e., adenylate cyclase) and degradation (i.e., cyclic nucleotide phosphodiesterase). Additional linkage between the nervous and endocrine systems is evident from the fact that both systems are responsive to some of the same peptide messengers. For example, insulin, glucagon, angiotensin, and somatostatin have been found in the brain, and may function as neurotransmitters (Malencik and Anderson, 1982) perhaps through CaM mediation.

Keywords:   SDS, amphipathic helix, cAMP, calmodulin, mastoparan

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