Effects of Glycosylation on Peptide Conformation:  A Synergistic Experimental and Computational Study

Bosques, Carlos J.; Tschampel, Sarah M.; Woods, Robert J.; Imperiali, Barbara

doi:10.1021/ja0496266

Cited by 122 publications

(105 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Addition of bulky polar carbohydrate chains can modify the properties of the polypeptide (7,70). Glycosylation can affect the local secondary structure of proteins by stabilizing the conformation of residues proximal to the glycosylation site (42).…”

Section: Role Of N-glycans In Protein Folding Stability and Qualitymentioning

confidence: 99%

Role of N-glycosylation in trafficking of apical membrane proteins in epithelia

Vagin

Kraut²,

Sachs³

2009

American Journal of Physiology-Renal Physiology

168

157

View full text Add to dashboard Cite

ized distribution of plasma membrane transporters and receptors in epithelia is essential for vectorial functions of epithelia. This polarity is maintained by sorting of membrane proteins into apical or basolateral transport containers in the transGolgi network and/or endosomes followed by their delivery to the appropriate plasma membrane domains. Sorting depends on the recognition of sorting signals in proteins by specific sorting machinery. In the present review, we summarize experimental evidence for and against the hypothesis that N-glycans attached to the membrane proteins can act as apical sorting signals. Furthermore, we discuss the roles of N-glycans in the apical sorting event per se and their contribution to folding and quality control of glycoproteins in the endoplasmic reticulum or retention of glycoproteins in the plasma membrane. Finally, we review existing hypotheses on the mechanism of apical sorting and discuss the potential roles of the lectins, VIP36 and galectin-3, as putative apical sorting receptors. apical sorting; apical membrane retention; H-K-ATPase ␤-subunit; lectin EPITHELIAL CELLS CARRY OUT vectorial transport that requires polarized distribution of transporters and receptors to apical or basolateral membrane domains. These domains are separated by tight junctions that connect neighboring cells in the epithelial monolayer and act as diffusion barriers to prevent mixing of apical and basolateral membrane components (22). Asymmetric distribution of plasma membrane proteins is accomplished by their sorting into apical and basolateral containers in the trans-Golgi network (TGN) and/or endosomes followed by vectorial transport of these containers and insertion and retention of the proteins in the appropriate plasma membrane domains. Sorting depends on recognition of apical and basolateral sorting signals within the proteins by cellular sorting machinery (20,58,59,75,76).Numerous studies have indicated that both O-and N-glycans attached to the extracellular domains of some membrane proteins are important for apical location of these proteins. This review will focus on the role of N-glycans in polarized distribution of plasma membrane proteins in epithelia. The role of O-glycans in apical sorting has been described in several recent excellent reviews (18, 71) and will not be discussed further here.A putative role of N-glycans as apical sorting signals was postulated more than 10 years ago (24, 31). However, this hypothesis remains controversial primarily because N-glycans are important for the processes that precede or follow the actual sorting event, such as protein folding, quality control, endoplasmic reticulum (ER)-associated degradation, ER-to-Golgi trafficking, and retention of glycoproteins in the apical membrane. Therefore, merely examining the effect of altering the number or the nature of N-linked glycans on the relative abundance of the glycoprotein in the apical membrane, as has been done in many of the studies reported, does not allow one to distinguish between effects on apica...

show abstract

Section: Role Of N-glycans In Protein Folding Stability and Qualitymentioning

confidence: 99%

Role of N-glycosylation in trafficking of apical membrane proteins in epithelia

Vagin

Kraut²,

Sachs³

2009

American Journal of Physiology-Renal Physiology

168

157

View full text Add to dashboard Cite

show abstract

“…This regulation can occur at multiple levels, including expression of the protease genes, secretion, processing of an inactive secreted precursor to its active form and/or the posttranslational glycosylation of the proteins (Gallagher et al, 2003;Bosques et al, 2004). The multiple layers of regulation are vital to ensure that expression is tightly controlled in the appropriate temporal and spatial patterns.…”

Section: Introductionmentioning

confidence: 99%

VimA is part of the maturation pathway for the major gingipains of Porphyromonas gingivalis W83

et al. 2006

View full text Add to dashboard Cite

The authors have shown previously that the vimA gene, which is part of the bcp-recA-vimA operon, plays an important role in protease activation in Porphyromonas gingivalis. The gingipain RgpB proenzyme is secreted in the vimA-defective mutant P. gingivalis FLL92. An important question that is raised is whether the vimA gene product could directly interact with the proteases for their activation or regulate a pathway responsible for protease activation. To further study the mechanism(s) of VimA-dependent protease activation, the vimA gene product was further characterized. A 39 kDa protein consistent with the size of the predicted VimA protein was purified. In protein–protein interaction studies, the VimA protein was shown to interact with gingipains RgpA, RgpB and Kgp. Immune sera from mice immunized with P. gingivalis immunoreacted with the purified VimA protein. Taken together, these data suggest an interaction of VimA with the gingipains and further confirm the role of this protein in their regulation or maturation.

show abstract

“…The N-linked oligosaccharide, or N-glycan, promotes glycoprotein folding in the endoplasmic reticulum by allowing the glycoprotein to enter the calnexin/calreticulin-assisted folding vs. degradation cycle (5,6). Glycans can also intrinsically accelerate protein folding (7,8), promote secondary structure formation (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24), and increase protein thermodynamic stability (8,25,26), but the molecular basis for these effects is incompletely understood (27).…”

mentioning

confidence: 99%

Glycosylation of the enhanced aromatic sequon is similarly stabilizing in three distinct reverse turn contexts

Price

Powers

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

146

View full text Add to dashboard Cite

Cotranslational N-glycosylation can accelerate protein folding, slow protein unfolding, and increase protein stability, but the molecular basis for these energetic effects is incompletely understood. N-glycosylation of proteins at naïve sites could be a useful strategy for stabilizing proteins in therapeutic and research applications, but without engineering guidelines, often results in unpredictable changes to protein energetics. We recently introduced the enhanced aromatic sequon as a family of portable structural motifs that are stabilized upon glycosylation in specific reverse turn contexts: a five-residue type I β-turn harboring a G1 β-bulge (using a Phe-Yyy-Asn-Xxx-Thr sequon) and a type II β-turn within a sixresidue loop (using a Phe-Yyy-Zzz-Asn-Xxx-Thr sequon) [Culyba EK, et al. (2011) Science 331:571-575]. Here we show that glycosylating a new enhanced aromatic sequon, Phe-Asn-Xxx-Thr, in a type I′ β-turn stabilizes the Pin 1 WW domain. Comparing the energetic effects of glycosylating these three enhanced aromatic sequons in the same host WW domain revealed that the glycosylation-mediated stabilization is greatest for the enhanced aromatic sequon complementary to the type I β-turn with a G1 β-bulge. However, the portion of the stabilization from the tripartite interaction between Phe, Asn(GlcNAc), and Thr is similar for each enhanced aromatic sequon in its respective reverse turn context. Adding the Phe-Asn-Xxx-Thr motif (in a type I′ β-turn) to the enhanced aromatic sequon family doubles the number of proteins that can be stabilized by glycosylation without having to alter the native reverse turn type.glycoprotein | biopharmaceutical | conjugate | native state stabilization | β-sheet

show abstract

Effects of Glycosylation on Peptide Conformation: A Synergistic Experimental and Computational Study

Cited by 122 publications

References 25 publications

Role of N-glycosylation in trafficking of apical membrane proteins in epithelia

Role of N-glycosylation in trafficking of apical membrane proteins in epithelia

VimA is part of the maturation pathway for the major gingipains of Porphyromonas gingivalis W83

Glycosylation of the enhanced aromatic sequon is similarly stabilizing in three distinct reverse turn contexts

Contact Info

Product

Resources

About