Huntingtin

Huntingtin (HTT) is a large (350 kDa) protein essential for embryonic development and is involved in a variety of cellular functions, such as vesicular transport, endocytosis, transcription regulation and autophagy. Mutation in the associated gene — IT15 — results in an expansion of the polyQ tract found within the N-terminal region of the perspective protein. Such pathological growth, which surpasses the treshold of 36 glutamine residues, may lead to the development of Huntington disease (HD). The mutation becomes fully penetrant at ≥40 glutamine residues ^[1]. Mutant huntingtin (mHTT) is prone to aggregation. Yet, despite its ubiquitous expression, mHTT affects primarily the GABAergic medium spiny neurons of striatum and to a lesser extent the neurons of cerebral cortex ^[2].

Function

Since the discovery of HTT and its relevance to HD, efforts have been made to understand the physiological functions of wild-type huntingtin. However, an integrative understanding of its biological functions is still lacking. Many studies suggest that HTT is essential for cell survival and thereby its loss of function caused by the mutation is source for the neurodegeneration. Although it does, up to a certain degree, add to the disease phenotype, it is now generally believed that the main source of the disease is not the loss of its physiological functions, but the gain of function associated with the polyQ expansion.

Huntingtin and embryonic development

The crucial role of HTT for embryonic development has been shown using mouse knock-out (KO) models, in which homozygous KO mice die at day 8.5 and don't emerge the nervous system. ^[3]

Disease

Relevance

Structural highlights

This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.