Crystal structures of the human Dysferlin inner DysF domain

BMC Structural Biology

Nicholas H Keep³  Christine Orengo¹  Corin Yeats²  Ambrose R Cole³  Altin Sula³ 

[1] Structural & Molecular Biology, Darwin Building, Institute for Structural and Molecular Biology , University College London, Gower Street, London WC1E 6BT, UK;Current Address: Infectious Disease Epidemiology, Imperial College London, St Mary’s Campus, Norfolk Place, London W2 1PG, UK;Crystallography, Biological Sciences, Institute for Structural and Molecular Biology, Birkbeck University of London, Malet Street, London WC1E 7HX, UK

关键词: Crystal structure;    DysF domain;    Arginine-tryptophan stacking;    Limb girdle muscular dystrophy 2B;    Dysferlin;   

Others  :  1090956
DOI  :  10.1186/1472-6807-14-3

 received in 2013-11-12, accepted in 2014-01-15,  发布年份 2014

【 摘 要 】

Background

Mutations in dysferlin, the first protein linked with the cell membrane repair mechanism, causes a group of muscular dystrophies called dysferlinopathies. Dysferlin is a type two-anchored membrane protein, with a single C terminal trans-membrane helix, and most of the protein lying in cytoplasm. Dysferlin contains several C2 domains and two DysF domains which are nested one inside the other. Many pathogenic point mutations fall in the DysF domain region.

Results

We describe the crystal structure of the human dysferlin inner DysF domain with a resolution of 1.9 Ångstroms. Most of the pathogenic mutations are part of aromatic/arginine stacks that hold the domain in a folded conformation. The high resolution of the structure show that these interactions are a mixture of parallel ring/guanadinium stacking, perpendicular H bond stacking and aliphatic chain packing.

Conclusions

The high resolution structure of the Dysferlin DysF domain gives a template on which to interpret in detail the pathogenic mutations that lead to disease.

【 授权许可】

   
2014 Sula et al.; licensee BioMed Central Ltd.

【 图 表 】

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