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


     

Published online before print December 2, 2004, 10.1110/ps.04977905
Protein Science (2005), 14:89-96. Published by Cold Spring Harbor Laboratory Press. Copyright © 2005 The Protein Society
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
ps.04977905v1
14/1/89    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
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 HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chowdhury, F. A.
Right arrow Articles by Raleigh, D. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chowdhury, F. A.
Right arrow Articles by Raleigh, D. P.
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?

A comparative study of the {alpha}-subdomains of bovine and human {alpha}-lactalbumin reveals key differences that correlate with molten globule stability

Farhana A. Chowdhury1 and Daniel P. Raleigh1,2,3

1 Department of Chemistry, 2 Graduate Program in Biochemistry and Structural Biology, and 3 Graduate Program in Physiology and Biophysics, State University of New York at Stony Brook, Stony Brook, New York 11794-3400, USA

(RECEIVED July 7, 2004; FINAL REVISION September 6, 2004; ACCEPTED September 13, 2004)

The {alpha}-lactalbumins form stable molten globule states under a range of conditions, with the low pH form being the best characterized. The stability of the molten globule varies among different members of this family, but the origin of the stability difference is not clear. We compare the folding and stability of {alpha}-subdomain constructs of human and bovine {alpha}-lactalbumin. Previous studies have demonstrated that the isolated {alpha}-subdomain of human {alpha}-lactalbumin folds and forms a molten globule state. The minimum core construct has been defined to include the A, B, and D {alpha}-helices and the C-terminal 310 helix. A construct corresponding to the same region of bovine {alpha}-lactalbumin is much less structured and less stable than the human {alpha}-lactalbumin construct. Addition of the C-helix to generate a 75-residue bovine construct does not lead to a significant increase in structure or stability. This construct (AB-CD/310) contains the entire {alpha}-subdomain of bovine {alpha}-lactalbumin. Thus molten globule formation in the human protein, but not in the bovine protein, can be rationalized on the basis of a stable {alpha}-subdomain. Interactions involving more of the protein chain are required to generate a well structured molten globule in the bovine protein. Comparison of AB-CD/310 to the molten globule formed by the intact protein and to the protein with the 6–120 disulfide reduced indicates that both the {beta}-subdomain and the 6–120 disulfide play a role in stabilizing the bovine {alpha}-lactalbumin molten globule.

Keywords: A-state; {alpha}-lactalbumin; molten globule; partially folded states; protein folding; protein stability

Abbreviations: AB, a peptide corresponding to residues 1–38 of bovine {alpha}-lactalbumin • AB-CD/310, a peptide consisting of residues 1–38 of bovine {alpha}-lactalbumin cross-linked via the 28–111 disulfide to a peptide consisting of residues 84–120 of bovine {alpha}-lactalbumin • AB-D/310, a peptide corresponding to residues 1–38 of bovine {alpha}-lactalbumin cross-linked via the 28–111 disulfide to a peptide consisting of residues 95–120 of bovine {alpha}-lactalbumin • ANS, 1-anilinonapthalene-8-sulfonate • BLA6–120, bovine {alpha}-lactalbumin with the 6–120 disulfide selectively reduced and blocked by iodoacetamide • CD, circular dichroism • CD/310, a peptide corresponding to residues 84–120 of bovine {alpha}-lactalbumin • D/310, a peptide corresponding to residues 95–120 of bovine {alpha}-lactalbumin • GnHCl, guanidinium hydrochloride • HATU, N-[(dimethylamino)-1H-1,2,3-triazolo[4,5-b]pyridine-1-ylmethylene]-N-methylmethanaminium hexafluorophosphate N-oxide • HBTU, N-[(1H-benzotriazol-1 yl)(dimethylamino)methylene]-N-methyl-methanaminium hexafluorophosphate N-oxide • HPLC, high-pressure liquid chromatography • MALDI TOF, matrix-assisted laser desorption ionization time of flight mass spectrometry • PAL PEG, 5-(4'mino-methyl-3', 5'-dimethoxyphenoxy) valeryl polyethylene glycol • TFA, tri-fluoroacetic acid

Article published online ahead of print. Article and publication date are at http://www.proteinscience.org/cgi/doi/10.1110/ps.04977905.

Reprint requests to: Daniel Raleigh, Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794-3400, USA; e-mail: draleigh{at}notes.cc.sunysb.edu; fax: (631) 632-7960.


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?


This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
K. H. Mok, T. Nagashima, I. J. Day, P. J. Hore, and C. M. Dobson
Multiple subsets of side-chain packing in partially folded states of {alpha}-lactalbumins
PNAS, June 21, 2005; 102(25): 8899 - 8904.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2005 by The Protein Society.