A Critical Residue in the Folding Pathway of an Integral Membrane Protein

Although a number of common diseases are a direct consequence of membrane protein misfolding, studies of membrane protein folding and misfolding lag well behind those of soluble proteins. Here it is shown that an interfacial residue, Tyr16, of the integral membrane protein diacylglycerol kinase (DAG...

Full description

Saved in:
Bibliographic Details
Published in:Biochemistry (Easton) 2002-07, Vol.41 (29), p.9021-9025
Main Authors: Nagy, Joanna K, Sanders, Charles R
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Diacylglycerol Kinase - chemistry
Diacylglycerol Kinase - metabolism
Electrophoresis, Polyacrylamide Gel
Enzyme Stability
Escherichia coli - enzymology
Kinetics
Molecular Sequence Data
Protein Folding
Thermodynamics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Although a number of common diseases are a direct consequence of membrane protein misfolding, studies of membrane protein folding and misfolding lag well behind those of soluble proteins. Here it is shown that an interfacial residue, Tyr16, of the integral membrane protein diacylglycerol kinase (DAGK) plays a critical role in the folding pathway of this protein. Properly folded Y16C exhibits kinetic parameters and stability similar to wild-type DAGK. However, when unfolded and then allowed to spontaneously fold in the presence of model membranes, Y16C exhibits dramatically lower rates and efficiencies of functional assembly compared to the wild-type protein. The Y16C mutant represents a class of mutations which may be commonly found in disease-related membrane proteins.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi020318z