Structure of the N-terminal domain of GRP94. Basis for ligand specificity and regulation.
GRP94, the endoplasmic reticulum (ER) paralog of the chaperone Hsp90, plays an essential role in the structural maturation or secretion of a subset of proteins destined for transport to the cell surface, such as the Toll-like receptors 2 and 4, and IgG, respectively. GRP94 differs from cytoplasmic Hsp90 by exhibiting very weak ATP binding and hydrolysis activity. GRP94 also binds selectively to a series of substituted adenosine analogs. The high resolution crystal structures at 1.75-2.1 A of the N-terminal and adjacent charged domains of GRP94 in complex with N-ethylcarboxamidoadenosine, radicicol, and 2-chlorodideoxyadenosine reveals a structural mechanism for ligand discrimination among hsp90 family members. The structures also identify a putative subdomain that may act as a ligand-responsive switch. The residues of the charged region fold into a disordered loop whose termini are ordered and continue the twisted beta sheet that forms the structural core of the N-domain. This continuation of the beta sheet past the charged domain suggests a structural basis for the association of the N-terminal and middle domains of the full-length chaperone.
Duke Scholars
Altmetric Attention Stats
Dimensions Citation Stats
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Substrate Specificity
- Sequence Homology, Amino Acid
- Recombinant Fusion Proteins
- Protein Structure, Tertiary
- Protein Conformation
- Protein Binding
- Molecular Sequence Data
- Models, Molecular
- Models, Chemical
- Membrane Proteins
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Substrate Specificity
- Sequence Homology, Amino Acid
- Recombinant Fusion Proteins
- Protein Structure, Tertiary
- Protein Conformation
- Protein Binding
- Molecular Sequence Data
- Models, Molecular
- Models, Chemical
- Membrane Proteins