Document Detail


HIV Rev self-assembly is linked to a molten-globule to compact structural transition.
MedLine Citation:
PMID:  15043924     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
By regulating the differential expression of proviral pre mRNA in the host cell, Rev plays a crucial role in the HIV-1 life cycle. The capacity of Rev to function is intimately linked to its ability to self-associate. Nevertheless, little is known about the exact role of self-association in the molecular mechanism defining its biological activity. A prerequisite knowledge is a definition of the molecular events undertaken by Rev during the process of self-assembly. Thus, this study was initiated to monitor the structure of Rev as a function of protein concentration. Rev undergoes a structural transition as a consequence of self-assembly. This structural transition was monitored by three spectroscopic methods. The accessibility of the single tryptophan in Rev monomer to acrylamide quenching increases with decreasing protein concentration. At very low concentration of Rev, the tryptophan accessibility is close to that of an unfolded Rev. As evaluated by circular dichroism, the secondary structure of Rev is protein concentration dependent as evidenced by an increase in the magnitude of ellipticity with increasing protein concentration. Further, results from ANS binding studies indicate that the ANS binding sites in Rev experience an apparent increase in hydrophobicity as the Rev concentration was increased. These concentration dependent changes seem to reach a maximum above 5 microM Rev monomer concentration. In order to define the mode of Rev self-association sedimentation velocity and equilibrium experiments were conducted. There are evidently two consecutive progressive association processes. At protein concentrations below 0.5 mg/ml, the data from sedimentation studies can be fitted to a single isodesmic model. Simulation of velocity sedimentation profile indicates that free Rev monomer that has not entered into the association processes can best be described to exhibit a value of S(20,w) that is substantially smaller than 1.4 S, a value needed to fit the rest of the data. The latter value is consistent for a Rev monomer with the expected molecules weight and if it were to assume a compact globular shape. These spectroscopic and hydrodynamic results imply that monomeric Rev is in a molten globule state, which becomes more compact upon self-association.
Authors:
Rajendran Surendran; Petr Herman; Zhijie Cheng; Thomas J Daly; J Ching Lee
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biophysical chemistry     Volume:  108     ISSN:  0301-4622     ISO Abbreviation:  Biophys. Chem.     Publication Date:  2004 Mar 
Date Detail:
Created Date:  2004-03-26     Completed Date:  2004-09-09     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0403171     Medline TA:  Biophys Chem     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  101-19     Citation Subset:  IM    
Affiliation:
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, Texas 77555-1055, USA.
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MeSH Terms
Descriptor/Qualifier:
Acrylamide / chemistry
Binding Sites
Circular Dichroism
Cloning, Molecular
Escherichia coli
Gene Products, rev / chemistry*,  isolation & purification,  metabolism
HIV-1 / chemistry*
Hydrogen-Ion Concentration
Hydrophobicity
Protein Denaturation
Protein Folding
Sodium Chloride / chemistry
Spectrometry, Fluorescence
Thermodynamics
Tryptophan / chemistry
rev Gene Products, Human Immunodeficiency Virus
Grant Support
ID/Acronym/Agency:
GM-45579/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Gene Products, rev; 0/rev Gene Products, Human Immunodeficiency Virus; 73-22-3/Tryptophan; 7647-14-5/Sodium Chloride; 79-06-1/Acrylamide

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