Probing into the role of conserved N-glycosylation sites in the Tyrosinase glycoprotein family Garima Gupta & Sharmistha Sinha & Nivedita Mitra & Avadhesha Surolia Received: 30 April 2008 / Revised: 8 September 2008 / Accepted: 28 October 2008 / Published online: 13 November 2008 # Springer Science + Business Media, LLC 2008 Abstract N-linked glycosylation has a profound effect on the proper folding, oligomerization and stability of glycoproteins. These glycans impart many properties to proteins that may be important for their proper functioning, besides having a tendency to exert a chaperone-like effect on them. Certain glycosylation sites in a protein however, are more important than other sites for their function and stability. It has been observed that some N-glycosylation sites are conserved over families of glycoproteins over evolution, one such being the tyrosinase related protein family. The role of these conserved N-glycosylation sites in their trafficking, sorting, stability and activity has been examined here. By scrutinizing the different glycosylation sites on this family of glycoproteins it was inferred that different sites in the same family of polypeptides can perform distinct functions and conserved sites across the paralogues may perform diverse functions. Keywords N-linked glycosylation . Tyrosinase . TRP-1 . TRP-2 Introduction Post-translational modification of proteins is a common event in eukaryotic cells, of which, glycosylation is the most frequent [1]. The complex glycans may be attached to proteins by three distinct types of modifications; namely N-linked glycosylation of asparagines, O-linked glycosylation of serine or threonine and glycosylphosphatidylinositol derivatization of the carboxy-terminal end [2–4]. For a long time, the role of glycosylation of proteins was ambiguous. In the past two decades, significant development in the field of glycobiology has shed light on its importance. Glycosylation protects proteins from proteolytic degradation. Also, it is an efficient method to generate diversity as the glycans possess inherent structural variation. Of particular importance is modification by N-glycosylation. It is now known that N-linked carbohy- drates play important roles in diverse biological processes such as protein folding and conformation, targeting of proteins to subcellular locations and extracellular sites (quality control), as well as cell–cell interactions [5–7]. Many studies show that they have a crucial role to play in cell-cycle progression and are essential for cell viability. Furthermore, many players of immune system, such as cytokines, anti- bodies and cellular receptors, are N-glycosylated [8–10]. Based on various biochemical, biophysical as well as genetic studies, it is currently acknowledged that N-glycosyl- ation greatly influences the conformational dynamics of nascent polypeptide chains [11]. The increased efficiency of folding of glycosylated proteins may be a result of “chaper- one-like” activity of glycans. Presence of glycans enhances the probability of achieving a correctly-folded conformation. Furthermore, covalently linked glycans also facilitate protein oligomerization by mediating the inter-subunit interactions and stabilizing the oligomer [12–18]. However, it is undetermined whether there exists any correlation among the sites of glycosylation and the subsequent effect in multiple-times glycosylated proteins; whether there is any pattern common to the conservation of glycans in a related family of glycoproteins. Most families of proteins that undergo N-glycosylation have conserved set(s) of asparagine residues that can be Glycoconj J (2009) 26:691–695 DOI 10.1007/s10719-008-9213-x G. Gupta : S. Sinha : N. Mitra : A. Surolia Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India A. Surolia (*) National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India e-mail: surolia@nii.res.in