1ji9

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Solution structure of the alpha-domain of mouse metallothionein-3

Overview

The brain specific member of the metallothionein (MT) family of proteins, metallothionein-3, inhibits the growth and survival of neurons, in, contrast to the ubiquitous mammalian MT isoforms, MT-1 and MT-2, that are, found in most tissues and are thought to function in metal ion homeostasis, and detoxification. Solution NMR was utilized to determine the structural, and dynamic differences of MT-3 from MT-1 and 2. The high-resolution, solution structure of the C-terminal alpha-domain of recombinant mouse, MT-3 revealed a tertiary fold very similar to MT-1 and 2, except for a, loop that accommodates an acidic insertion relative to these isoforms., This loop was distinguished from the rest of the domain by dynamics of the, backbone on the nano- to picosecond time-scale shown by (15)N relaxation, studies and was identified as a possible interaction site with other, proteins. The N-terminal beta-domain contains the region responsible for, the growth inhibitory activity, a CPCP tetrapeptide close to the, N-terminus. Because of exchange broadening of a large number of the NMR, signals from this domain, homology modeling was utilized to calculate, models for the beta-domain and suggested that while the backbone fold of, the MT-3 beta-domain is identical to MT-1 and 2, the second proline, responsible for the activity, Pro9, may show structural heterogeneity., (15)N relaxation analyses implied fast internal motions for the, beta-domain. On the basis of these observations, we conclude that the, growth inhibitory activity exhibited by MT-3 is a result of a combination, of local structural differences and global dynamics in the beta-domain.

About this Structure

1JI9 is a Single protein structure of sequence from Mus musculus with CD as ligand. Full crystallographic information is available from OCA.

Reference

Three-dimensional structure and dynamics of a brain specific growth inhibitory factor: metallothionein-3., Oz G, Zangger K, Armitage IM, Biochemistry. 2001 Sep 25;40(38):11433-41. PMID:11560491

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