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1qzp
From Proteopedia
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NMR structure of the human dematin headpiece domain
Contents |
Overview
Dematin (band 4.9) is found in the junctional complex of the spectrin cytoskeleton that supports the erythrocyte cell membrane. Dematin is a member of the larger class of cytoskeleton-associated proteins that contain a modular "headpiece" domain at their extreme C termini. The dematin headpiece domain provides the second F-actin-binding site required for in vitro F-actin bundling. The dematin headpiece is found in two forms in the cell, one of 68 residues (DHP) and one containing a 22-amino acid insert near its N terminus (DHP+22). In addition, dematin contains the only headpiece domain that is phosphorylated, in vivo. The 22-amino acid insert in DHP+22 appeared unstructured in NMR spectra; therefore, we have determined the three-dimensional structure of DHP by multidimensional NMR methods. Although the overall three-dimensional structure of DHP is similar to that of the villin headpiece, there are two novel characteristics revealed by this structure. First, unlike villin headpiece that contains a single buried salt bridge, DHP contains a buried charged cluster comprising residues Glu(39), Arg(66), Lys(70), and the C-terminal carboxylate of Phe(76). Second, (15)N relaxation experiments indicate that the longer "variable loop" region near the N terminus of DHP (residues 20-29) is dynamic, undergoing significantly greater motions that the rest of the structure. Furthermore, NMR chemical shift changes indicate that the conformation of the dynamic variable loop is altered by phosphorylation of serine 74, which is far in the sequence from the variable loop region. Our results suggest that phosphorylation of the dematin headpiece acts as a conformational switch within this headpiece domain.
Disease
Known diseases associated with this structure: Amyotrophic lateral sclerosis, CHMP2B-related OMIM:[609512], Dementia, familial, nonspecific OMIM:[609512], XY sex reversal OMIM:[602424]
About this Structure
1QZP is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The NMR structure of dematin headpiece reveals a dynamic loop that is conformationally altered upon phosphorylation at a distal site., Frank BS, Vardar D, Chishti AH, McKnight CJ, J Biol Chem. 2004 Feb 27;279(9):7909-16. Epub 2003 Dec 2. PMID:14660664
Page seeded by OCA on Thu Feb 21 14:45:31 2008
