title: Melanosomal proteins promote melanin polymerization.
abstract: In melanocytes, enzymes involved in the generation of melanin monomers are present and active in coated vesicles which are known to be acidic. Melanin polymerization however, occurs only in melanosomes. In vitro, it is not possible to generate melanin at the acidic pH of melanosomes using 3,4-dihydroxyphenylalanine (DOPA) and tyrosinase alone whereas melanin readily forms at higher pH with these reagents. Dimerization and elongation of the melanin polymer is known to require deprotonation. We have hypothesized that the amino acid side chains of melanosomal proteins act as proton acceptors to initiate polymerization and that the protonated basic groups serve to attract the negatively charged oligomers thus aiding polymerization and binding to proteins. We show that basic model proteins and basic premelanosomal proteins promote polymerization at an acidic pH and that positively charged surfaces allow binding of the growing melanin polymer. With progressive polymerization and exhaustion of the proton abstracting ability of melanosomal proteins, melanosomal pH drops further, which, we argue, is an additional controlling step that limits tyrosinase activity and melanin polymerization.
authors.affiliation: Hindustan Lever Research Centre, Andheri [E], Mumbai, India.
authors.forename: S
authors.initials: S
authors.lastname: Wagh
authors.forename: A
authors.initials: A
authors.lastname: Ramaiah
authors.forename: R
authors.initials: R
authors.lastname: Subramanian
authors.forename: R
authors.initials: R
authors.lastname: Govindarajan
mesh_terms: D000818:Animals; D000837:Anion Exchange Resins / Q000737:chemistry; D002417:Cattle; D002848:Chromatography, DEAE-Cellulose; D002852:Chromatography, Ion Exchange; D004305:Dose-Response Relationship, Drug; D006863:Hydrogen-Ion Concentration; D008543:Melanins / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000378:metabolism; D020460:Melanosomes / Q000378:metabolism*; D051379:Mice; D008855:Microscopy, Electron, Scanning; D014442:Monophenol Monooxygenase / Q000378:metabolism; D009113:Muramidase / Q000378:metabolism; D009492:Neurospora crassa / Q000201:enzymology; D011485:Protein Binding; D012117:Resins, Synthetic; D012709:Serum Albumin / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000837:Anion Exchange Resins; D008543:Melanins; D012117:Resins, Synthetic; D012709:Serum Albumin; C027972:Dowex; D014442:Monophenol Monooxygenase; D009113:Muramidase