Maximum occurrence analysis of protein conformations for different distributions of paramagnetic metal ions within flexible two-domain proteins

• Published in: Journal of magnetic resonance (1997) Vol. 215; pp. 85 - 93
• Main Authors: Luchinat, Claudio, Nagulapalli, Malini, Parigi, Giacomo, Sgheri, Luca
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-02-2012
• Subjects: Algorithms; Anisotropy; Calmodulin - chemistry; Data Interpretation, Statistical; Electromagnetic Fields; Electron Spin Resonance Spectroscopy; Lanthanoid Series Elements; Maximum occurrence; Metals - chemistry; Models, Molecular; Paramagnetic residual dipolar couplings; Paramagnetic restraints; Protein Conformation; Protein mobility; Protein Structure, Tertiary; Proteins - chemistry; Pseudocontact shifts; Paramagnetic restraints; Maximum occurrence; Paramagnetic residual dipolar couplings; Protein mobility; Pseudocontact shifts
• ISSN: 1090-7807; 1096-0856
• DOI: 10.1016/j.jmr.2011.12.016

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► Paramagnetic metals within a protein provide pcs and paramagnetic rdc. ► Two-domain proteins with a flexible linker can sample multiple conformations. ► Pcs and paramagnetic rdc provide the maximum occurrence of each conformation. ► A compatibility index is defined if paramagnetic metals are bound in both domains.
Multidomain proteins are composed of rigid domains connected by (flexible) linkers. Therefore, the domains may experience a large degree of reciprocal reorientation. Pseudocontact shifts and residual dipolar couplings arising from one or more paramagnetic metals successively placed in a single metal binding site in the protein can be used as restraints to assess the degree of mobility of the different domains. They can be used to determine the maximum occurrence (MO) of each possible protein conformation, i.e. the maximum weight that such conformations can have independently of the real structural ensemble, in agreement with the provided restraints. In the case of two-domain proteins, the metal ions can be placed all in the same domain, or distributed between the two domains. It has been demonstrated that the quantity of independent information for the characterization of the system is larger when all metals are bound in the same domain. At the same time, it has been shown that there are practical advantages in placing the metals in different domains. Here, it is shown that distributing the metals between the domains provides a tool for defining a coefficient of compatibility among the restraints obtained from different metals, without a significant decrease of the capability of the MO values to discriminate among conformations with different weights.