5ttr: Difference between revisions

[[Image:5ttr.gif|left|200px]]<br /><applet load="5ttr" size="350" color="white" frame="true" align="right" spinBox="true"  

The x-ray crystal structure of the amyloidogenic Leu55 --&gt; Pro transthyretin (TTR) variant, implicated as the causative agent in early-onset familial amyloidotic polyneuropathy (Jacobson, D. R., McFarlin, D. E., Kane, I., and Buxbaum, J. N. (1992) Hum. Genet. 89, 353-356), has been solved by molecular replacement, refined at 2.7 A to a Rcryst value of 0.190 (Fobs &gt; 2.0sigma), and compared with wild-type transthyretin to understand the molecular mechanism(s) involved in amyloidogenesis. Leu55 --&gt; Pro TTR crystallizes in space group C2, with eight monomers in the asymmetric unit, and the observed packing contacts are considerably different from those described for the wild-type protein. Refinement of the crystal structure shows that the proline for leucine substitution disrupts the hydrogen bonds between strands D and A, resulting in different interface contacts. Based on the assumption that the observed packing contacts may be significant for amyloidogenesis, a model for the TTR amyloid is proposed. It consists of a tubular structure with inner and outer diameters approximately of 30 and 100 A and four monomers per cross-section.

5TTR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TTR OCA].  

[[Category: Damas, A M.]]

[[Category: Saraiva, M J.]]

[[Category: Sebastiao, M P.]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:15:58 2008''