1sw8

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Solution structure of the N-terminal domain of Human N60D calmodulin refined with paramagnetism based strategy

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The conformational space sampled by the two-domain protein calmodulin has, been explored by an approach based on four sets of NMR observables, obtained on Tb(3+)- and Tm(3+)-substituted proteins. The observables are, the pseudocontact shifts and residual dipolar couplings of the C-terminal, domain when lanthanide substitution is at the N-terminal domain. Each set, of observables provides independent information on the conformations, experienced by the molecule. It is found that not all sterically allowed, conformations are equally populated. Taking the N-terminal domain as the, reference, the C-terminal domain preferentially resides in a region of, space inscribed in a wide elliptical cone. The axis of the cone is tilted, by approximately 30 degrees with respect to the direction of the, N-terminal part of the interdomain helix, which is known to have a, flexible central part in solution. The C-terminal domain also undergoes, rotation about the axis defined by the C-terminal part of the interdomain, helix. Neither the extended helix conformation initially observed in the, solid state for free calcium calmodulin nor the closed conformation(s), adopted by calcium calmodulin either alone or in its adduct(s) with target, peptide(s) is among the most preferred ones. These findings are unique, both in terms of structural information obtained on a biomolecule that, samples multiple conformations and in terms of the approach developed to, achieve the results. The same approach is in principle applicable to other, multidomain proteins, as well as to multiple interaction modes between two, macromolecular partners.

Disease

Known diseases associated with this structure: Cavernous malformations of CNS and retina OMIM:[604214], Cerebral cavernous malformations-1 OMIM:[604214], Hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformations OMIM:[604214], Leukemia, acute T-cell lymphoblastic OMIM:[603025], Leukemia, acute myeloid OMIM:[603025]

About this Structure

1SW8 is a Single protein structure of sequence from Homo sapiens with CA as ligand. Full crystallographic information is available from OCA.

Reference

Experimentally exploring the conformational space sampled by domain reorientation in calmodulin., Bertini I, Del Bianco C, Gelis I, Katsaros N, Luchinat C, Parigi G, Peana M, Provenzani A, Zoroddu MA, Proc Natl Acad Sci U S A. 2004 May 4;101(18):6841-6. Epub 2004 Apr 20. PMID:15100408

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