BP180/Collagen XVII: A Molecular View

Abstract

BP180 is a type II collagenous transmembrane protein and is best known as the major autoantigen in the blistering skin disease bullous pemphigoid (BP). The BP180 trimer is a central component in type I hemidesmosomes (HD), which cause the adhesion between epidermal keratinocytes and the basal lamina, but BP180 is also expressed in several non-HD locations, where its functions are poorly characterized. The immunological roles of intact and proteolytically processed BP180, relevant in BP, have been subject to intensive research, but novel functions in cell proliferation, differentiation, and aging have also recently been described. To better understand the multiple physiological functions of BP180, the focus should return to the protein itself. Here, we comprehensively review the properties of the BP180 molecule, present new data on the biochemical features of its intracellular domain, and discuss their significance with regard to BP180 folding and protein–protein interactions.

Insights Into the Pathogenesis of Bullous Pemphigoid: The Role of Complement-Independent Mechanisms

“…BP230, the epithelial isoform of BPAG1, is a cytoplasmic protein of the plakin family of cytolinkers. It primarily connects the keratin intermediate filament system to hemidesmosomes at the basal keratinocyte cell membrane ( 1 , 9 , 12 ). Patients’ sera recognize multiple antigenic regions on both target antigens, although the NC16A domain, on the extracellular membrane of BP180, contains the immunodominant antigenic determinants ( 13 , 14 ).…”

“…However, proteasomes may also be involved under certain circumstances, such as in relation to cross-presentation of antigens on the major histocompatibility complex I pathway ( 65 ). Hence, it remains unclear if BP180 is only degraded by proteasomal pathways or if lysosomes and/or other processes are also implicated ( 9 ).…”

“…BP180 is transmembrane protein with a large collagenous extra-cellular domain serving as an adhesion molecule. Its ectodomain binds to laminin 332 and type IV collagen, connecting the basal keratinocytes to the extracellular matrix of the epidermal basement membrane (9)(10)(11). BP230, the epithelial isoform of BPAG1, is a cytoplasmic protein of the plakin family of cytolinkers.…”

Einblicke in die Pathogenese des bullösen Pemphigoids: Die Rolle komplementunabhängiger Mechanismen

“…BP180 ist ein Transmembranprotein mit einer großen kollagenen extrazellulären Domäne, die als Adhäsionsmolekül dient. Seine Ektodomäne bindet an Laminin 332 und Kollagen Typ IV und verbindet die basalen Keratinozyten mit der extrazellulären Matrix der epidermalen Basalmembran [9-11]. BP230, die epitheliale Isoform von BPAG1, ist ein zytoplasmatisches Protein der Plakin-Familie von Zytolinkern.…”

Absence of NC14A Domain of COLXVII/BP180 in Mice Results in IL-17‒Associated Skin Inflammation

“…Collagen XVII (ColXVII/BP180), also known as BP180, is a transmembrane protein expressed in basal keratinocytes in the skin. ColXVII is a pivotal constituent of the hemidesmosomes, which bind the epidermis to the underlying basement membrane (Natsuga et al 2019;Tuusa et al 2021). Mutations in the COL17A1 gene result in one subtype of junctional epidermolysis bullosa (JEB), the symptoms of which include skin and mucosal blistering, skin atrophy, graying and loss of hair (Has et al 2018).…”