1JI9

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

Summary for 1JI9

• Entry DOI: 10.2210/pdb1ji9/pdb
• NMR Information: BMRB: 5066
• Descriptor: METALLOTHIONEIN-III, CADMIUM ION (2 entities in total)
• Functional Keywords: 3-10 helix, cd-s cluster, half turn, type ii turn, metal binding protein
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 1
• Total formula weight: 4250.12

Authors

Oz, G.,Zangger, K.,Armitage, I.M. (deposition date: 2001-07-01, release date: 2001-10-03, Last modification date: 2024-05-22)

Primary citation

Oz, G.,Zangger, K.,Armitage, I.M.
Three-dimensional structure and dynamics of a brain specific growth inhibitory factor: metallothionein-3.
Biochemistry, 40:11433-11441, 2001

PubMed Abstract: 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.

PubMed: 11560491
DOI: 10.1021/bi010827l

Experimental method

SOLUTION NMR