Protein Science
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Published online before print July 5, 2006
Protein Science, DOI: 10.1110/ps.062264006
 Copyright © 2006 The Protein Society
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
ps.062264006v1
15/8/1968    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sánchez-Puig, N.
Right arrow Articles by Fersht, A. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sánchez-Puig, N.
Right arrow Articles by Fersht, A. R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Characterization of the native and fibrillar conformation of the human N{alpha}-acetyltransferase ARD1

Nuria Sánchez-Puig1, and Alan R. Fersht

Centre for Protein Engineering, Medical Research Council, CB2 2QH Cambridge, United Kingdom

(RECEIVED April 3, 2006; FINAL REVISION May 17, 2006; ACCEPTED May 17, 2006)

ARD1 (arrest-defective protein 1), together with NAT1 (N-acetyltransferase protein 1), is part of the major N{alpha}-acetyltransferase complex in eukaryotes responsible for {alpha}-acetylation of proteins and peptides. Protein acetylation has been implicated in gene expression regulation and protein–protein interaction. We characterized the native folded and misfolded conformation of hARD1. Structural characterization of native hARD1 using size exclusion chromatography, circular dichroism, and fluorescence spectroscopy shows the protein consists of a compact globular region comprising two thirds of the protein and a flexible unstructured C terminus. In addition, hARD1 forms protofilaments under physiological conditions of pH and temperature, as judged by electron microscopy and staining with the dyes Congo red and thioflavin T. The process is accelerated by thermal denaturation and high protein concentrations. Limited proteolysis of aggregated hARD1 revealed a resistant fragment whose sequence matched a region contained within the acetyl transferase domain.

Keywords: ARD1; protofilaments; amyloid fibers

1 Present addresses: Laboratory of Molecular Biology, Medical Research Council, Hills Road, CB2 2QH Cambridge, United Kingdom; Department of Haematology, Cambridge Institute for Medical Research, Cambridge University, Hills Road, CB2 2XY Cambridge, United Kingdom.

Reprint requests to: Alan R. Fersht, Centre for Protein Engineering, Medical Research Council, Hills Road, CB2 2QH Cambridge, United Kingdom; e-mail: arf25{at}cam.ac.uk; fax: +44-1223-402140.

Article published online ahead of print. Article and publication date are at http://www.proteinscience.org/cgi/doi/10.1110/ps.062264006.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Copyright © 2006 by The Protein Society.