Cryo-EM structure of the extracellular domain of murine Thrombopoietin Receptor in complex with Thrombopoietin.

ABSTRACT: Thrombopoietin (Tpo) is the primary regulator of megakaryocyte and platelet numbers and is required for haematopoetic stem cell maintenance. Tpo functions by binding its receptor (TpoR, a homodimeric Class I cytokine receptor) and initiating cell proliferation or differentiation. Here we characterise the murine Tpo:TpoR signalling complex biochemically and structurally, using cryo-electron microscopy. Tpo uses opposing surfaces to recruit two copies of receptor, forming a 1:2 complex. Although it binds to the same, membrane-distal site on both receptor chains, it does so with significantly different affinities and its highly glycosylated C-terminal domain is not required. In one receptor chain, a large insertion, unique to TpoR, forms a partially structured loop that contacts cytokine. Tpo

SUBMITTER: Sarson-Lawrence KTG 

PROVIDER: S-EPMC10850085 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature