Scholars@Duke
Christopher Vincent Nicchitta

Christopher Vincent Nicchitta

James B. Duke Distinguished Professor of Cell Biology
Cell Biology
Duke Box 3709, Durham, NC 27710
436 Nanaline H Duke, Durham, NC 27708

Featured Works

Interaction of TLR2 and TLR4 ligands with the N-terminal domain of Gp96 amplifies innate and adaptive immune responses.

Journal article J Biol Chem · August 11, 2006 Featured Publication Activation of dendritic cells by ligands for Toll-like receptors (TLR) is a crucial event in the initiation of innate and adaptive immune responses. Several classes of TLR ligands have been identified that interact with distinct members of the TLR-family. ... Full text Link to item Cite

The DRiP hypothesis decennial: support, controversy, refinement and extension.

Journal article Trends Immunol · August 2006 Featured Publication In 1996, to explain the rapid presentation of viral proteins to CD8+ T cells, it was proposed that peptides presented by MHC class I molecules derive from defective ribosomal products (DRiPs), presumed to be polypeptides arising from in-frame translation t ... Full text Link to item Cite

Identification of novel quaternary domain interactions in the Hsp90 chaperone, GRP94.

Journal article Protein Sci · June 2006 Featured Publication The structural basis for the coupling of ATP binding and hydrolysis to chaperone activity remains a central question in Hsp90 biology. By analogy to MutL, ATP binding to Hsp90 is thought to promote intramolecular N-terminal dimerization, yielding a molecul ... Full text Link to item Cite

mRNA translation is compartmentalized to the endoplasmic reticulum following physiological inhibition of cap-dependent translation.

Journal article RNA · May 2006 Featured Publication Eukaryotic cells utilize a cycle of ribosome trafficking on the endoplasmic reticulum (ER) to partition mRNAs between the cytosol and ER compartments. In this process, ribosomes engaged in the synthesis of signal sequence-bearing proteins are trafficked to ... Full text Link to item Cite

Pathways for compartmentalizing protein synthesis in eukaryotic cells: the template-partitioning model.

Journal article Biochem Cell Biol · December 2005 Featured Publication mRNAs encoding signal sequences are translated on endoplasmic reticulum (ER) -- bound ribosomes, whereas mRNAs encoding cytosolic proteins are translated on cytosolic ribosomes. The partitioning of mRNAs to the ER occurs by positive selection; cytosolic ri ... Full text Link to item Cite

Stable ribosome binding to the endoplasmic reticulum enables compartment-specific regulation of mRNA translation.

Journal article Mol Biol Cell · December 2005 Featured Publication In eukaryotic cells, protein synthesis is compartmentalized; mRNAs encoding secretory/membrane proteins are translated on endoplasmic reticulum (ER)-bound ribosomes, whereas mRNAs encoding cytosolic proteins are translated on free ribosomes. mRNA partition ... Full text Link to item Cite

GRP94 (gp96) and GRP94 N-terminal geldanamycin binding domain elicit tissue nonrestricted tumor suppression.

Journal article J Exp Med · December 2, 2002 Featured Publication In chemical carcinogenesis models, GRP94 (gp96) elicits tumor-specific protective immunity. The tumor specificity of this response is thought to reflect immune responses to GRP94-bound peptide antigens, the cohort of which uniquely identifies the GRP94 tis ... Full text Link to item Cite

A platform for compartmentalized protein synthesis: protein translation and translocation in the ER.

Journal article Curr Opin Cell Biol · August 2002 Featured Publication Recent advances in the study of protein translocation across the membrane of the endoplasmic reticulum include insights into the mechanism of signal-sequence function. Biochemical and genetic studies have provided further evidence that lumenal proteins per ... Full text Link to item Cite

Endoplasmic reticulum-bound ribosomes reside in stable association with the translocon following termination of protein synthesis.

Journal article J Biol Chem · June 28, 2002 Featured Publication In current views, translation-coupled ribosome binding to the endoplasmic reticulum (ER) membrane is transient, with association occurring via the signal recognition particle pathway and dissociation occurring upon the termination of protein synthesis. Rec ... Full text Link to item Cite

Transfer of GRP94(Gp96)-associated peptides onto endosomal MHC class I molecules.

Journal article Traffic · May 2002 Featured Publication GRP94 (gp96)-associated peptides can elicit cellular immune responses, an activity thought to reflect the presence of a cell surface receptor (CD91) on antigen-presenting cells that mediates GRP94 internalization and trafficking to an amenable site for pep ... Full text Link to item Cite

Cutting edge: CD91-independent cross-presentation of GRP94(gp96)-associated peptides.

Journal article J Immunol · May 1, 2002 Featured Publication GRP94(gp96) elicits CD8(+) T cell responses against its bound peptides, a process requiring access of its associated peptides into the MHC class I cross-presentation pathway of APCs. Entry into this pathway requires receptor-mediated endocytosis, and CD91 ... Full text Link to item Cite

Ribosome exchange revisited: a mechanism for translation-coupled ribosome detachment from the ER membrane.

Journal article Trends Cell Biol · March 2001 Featured Publication In current models, ribosome release from the endoplasmic reticulum (ER) is coupled to the termination of protein translation. Thus, coincident with termination, membrane-bound ribosomes dissociate into their component subunits and are released into the cyt ... Full text Link to item Cite

Regulation of ribosome detachment from the mammalian endoplasmic reticulum membrane.

Journal article J Biol Chem · October 27, 2000 Featured Publication In current models, protein translocation in the endoplasmic reticulum (ER) occurs in the context of two cycles, the signal recognition particle (SRP) cycle and the ribosome cycle. Both SRP and ribosomes bind to the ER membrane as a consequence of the targe ... Full text Link to item Cite

Ligand interactions in the adenosine nucleotide-binding domain of the Hsp90 chaperone, GRP94. I. Evidence for allosteric regulation of ligand binding.

Journal article J Biol Chem · July 28, 2000 Featured Publication X-ray crystallographic studies of the N-terminal domain of Hsp90 have identified an unconventional ATP binding fold, thereby inferring a role for ATP in the regulation of the Hsp90 activity. In this report, N-ethylcarboxamidoadenosine (NECA) was used to in ... Full text Link to item Cite

Ligand interactions in the adenosine nucleotide-binding domain of the Hsp90 chaperone, GRP94. II. Ligand-mediated activation of GRP94 molecular chaperone and peptide binding activity.

Journal article J Biol Chem · July 28, 2000 Featured Publication The N-terminal domain of eukaryotic Hsp90 proteins contains a conserved adenosine nucleotide binding pocket that also serves as the binding site for the Hsp90 inhibitors geldanamycin and radicicol. Although this domain is essential for Hsp90 function, the ... Full text Link to item Cite

The immunological properties of endoplasmic reticulum chaperones: a conflict of interest?

Journal article Essays Biochem · 2000 Featured Publication ER chaperones are abundant and highly conserved proteins that display both peptide binding and chaperone activity. Of the family of chaperones present in the mammalian ER, GRP94 and calreticulin are apparently unique in their ability to elicit CD8+ T-cell ... Full text Link to item Cite