HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shinde, U. Articles by Inouye, M. Search for Related Content PubMed PubMed Citation Articles by Shinde, U. Articles by Inouye, M. Social Bookmarking                      What's this?

J Biol Chem, Vol. 274, Issue 22, 15615-15621, May 28, 1999

A Pathway for Conformational Diversity in Proteins Mediated by Intramolecular Chaperones

From the Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854

Conformational diversity within unique amino acid sequences is observed in diseases like scrapie and Alzheimer's disease. The molecular basis of such diversity is unknown. Similar phenomena occur in subtilisin, a serine protease homologous with eukaryotic pro-hormone convertases. The subtilisin propeptide functions as an intramolecular chaperone (IMC) that imparts steric information during folding but is not required for enzymatic activity. Point mutations within IMCs alter folding, resulting in structural conformers that specifically interact with their cognate IMCs in a process termed "protein memory." Here, we show a mechanism that mediates conformational diversity in subtilisin. During maturation, while the IMC is autocleaved and subsequently degraded by the active site of subtilisin, enzymatic properties of this site differ significantly before and after cleavage. Although subtilisin folded by Ile⁴⁸  Thr IMC (IMC^I-48T) acquires an "altered" enzymatically active conformation (Sub^I-48T) significantly different from wild-type subtilisin (Sub^WT), both precursors undergo autocleavage at similar rates. IMC cleavage initiates conformational changes during which the IMC continues its chaperoning function subsequent to its cleavage from subtilisin. Structural imprinting resulting in conformational diversity originates during this reorganization stage and is a late folding event catalyzed by autocleavage of the IMC.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				S.-N. Lee and I. Lindberg 7B2 Prevents Unfolding and Aggregation of Prohormone Convertase 2 Endocrinology, August 1, 2008; 149(8): 4116 - 4127. [Abstract] [Full Text] [PDF]

				K. Yasukawa, M. Kusano, and K. Inouye A new method for the extracellular production of recombinant thermolysin by co-expressing the mature sequence and pro-sequence in Escherichia coli Protein Eng. Des. Sel., August 1, 2007; 20(8): 375 - 383. [Abstract] [Full Text] [PDF]

				M. Takahashi, T. Sekine, N. Kuba, S. Nakamori, M. Yasuda, and H. Takagi The Production of Recombinant APRP, an Alkaline Protease Derived from Bacillus pumilus TYO-67, by In Vitro Refolding of Pro-enzyme Fixed on a Solid Surface J. Biochem., October 1, 2004; 136(4): 549 - 556. [Abstract] [Full Text] [PDF]

				W. R. Lyon and M. G. Caparon Trigger Factor-Mediated Prolyl Isomerization Influences Maturation of the Streptococcus pyogenes Cysteine Protease J. Bacteriol., June 15, 2003; 185(12): 3661 - 3667. [Abstract] [Full Text] [PDF]

				Y. Yabuta, E. Subbian, C. Oiry, and U. Shinde Folding Pathway Mediated by an Intramolecular Chaperone. A FUNCTIONAL PEPTIDE CHAPERONE DESIGNED USING SEQUENCE DATABASES J. Biol. Chem., April 18, 2003; 278(17): 15246 - 15251. [Abstract] [Full Text] [PDF]

				S. L. Haberichter, M. A. Jozwiak, J. B. Rosenberg, P. A. Christopherson, and R. R. Montgomery The Von Willebrand Factor Propeptide (VWFpp) Traffics an Unrelated Protein to Storage Arterioscler. Thromb. Vasc. Biol., June 1, 2002; 22(6): 921 - 926. [Abstract] [Full Text] [PDF]

				E. D. Anderson, S. S. Molloy, F. Jean, H. Fei, S. Shimamura, and G. Thomas The Ordered and Compartment-specific Autoproteolytic Removal of the Furin Intramolecular Chaperone Is Required for Enzyme Activation J. Biol. Chem., April 5, 2002; 277(15): 12879 - 12890. [Abstract] [Full Text] [PDF]

				S. J. Firbank, M. S. Rogers, C. M. Wilmot, D. M. Dooley, M. A. Halcrow, P. F. Knowles, M. J. McPherson, and S. E. V. Phillips From the Cover: Crystal structure of the precursor of galactose oxidase: An unusual self-processing enzyme PNAS, November 6, 2001; 98(23): 12932 - 12937. [Abstract] [Full Text] [PDF]

				Y. Kannan, Y. Koga, Y. Inoue, M. Haruki, M. Takagi, T. Imanaka, M. Morikawa, and S. Kanaya Active Subtilisin-Like Protease from a Hyperthermophilic Archaeon in a Form with a Putative Prosequence Appl. Envir. Microbiol., June 1, 2001; 67(6): 2445 - 2452. [Abstract] [Full Text]

				B. Ma, C.-J. Tsai, and R. Nussinov Binding and folding: in search of intramolecular chaperone-like building block fragments Protein Eng. Des. Sel., September 1, 2000; 13(9): 617 - 627. [Abstract] [Full Text] [PDF]

				S. L. Haberichter, S. A. Fahs, and R. R. Montgomery Von Willebrand factor storage and multimerization: 2 independent intracellular processes Blood, September 1, 2000; 96(5): 1808 - 1815. [Abstract] [Full Text] [PDF]

				M. M. Barnhart, J. S. Pinkner, G. E. Soto, F. G. Sauer, S. Langermann, G. Waksman, C. Frieden, and S. J. Hultgren PapD-like chaperones provide the missing information for folding of pilin proteins PNAS, June 14, 2000; (2000) 130183897. [Abstract] [Full Text]

				X. Fu, M. Inouye, and U. Shinde Folding Pathway Mediated by an Intramolecular Chaperone. THE INHIBITORY AND CHAPERONE FUNCTIONS OF THE SUBTILISIN PROPEPTIDE ARE NOT OBLIGATORILY LINKED J. Biol. Chem., May 26, 2000; 275(22): 16871 - 16878. [Abstract] [Full Text] [PDF]

				L. Muller, A. Cameron, Y. Fortenberry, E. V. Apletalina, and I. Lindberg Processing and Sorting of the Prohormone Convertase 2 Propeptide J. Biol. Chem., December 8, 2000; 275(50): 39213 - 39222. [Abstract] [Full Text] [PDF]

				Y. Yabuta, H. Takagi, M. Inouye, and U. Shinde Folding Pathway Mediated by an Intramolecular Chaperone. PROPEPTIDE RELEASE MODULATES ACTIVATION PRECISION OF PRO-SUBTILISIN J. Biol. Chem., November 21, 2001; 276(48): 44427 - 44434. [Abstract] [Full Text] [PDF]