Human Huntingtin Protein Structure Huntingtin’s polyQ tract begins at the eighteenth amino acid and is followed by a proline rich sequence (polyP) composed by 38 amino acids (Figure 4). (2018) used cryoelectron microscopy to determine the structure of full-length human HTT in a complex with HTT-associated protein-40 (HAP40; 305423) to an overall resolution of 4 angstroms.HTT is largely alpha-helical and consists of 3 major domains. Huntington protein has a tadpolelike head (green and orange) and tail (purple) structure. The decoded structure will now enable the protein's functional analysis. Mutations on a single gene, the huntingtin gene, lead to an incorrect form of the correspondent protein.

Thee Dimensional Protein Structure. The devastating neurodegenerative disorder Huntington's disease (HD) is caused by a mutation in a curious protein called huntingtin. 2 Publications

The normal function of the Huntingtin (HTT) protein is emerging. The polyP stretch is thought to be important in maintaining huntingtin in solution, as if it balances the polyQ extreme insolubility. Shuttles between cytoplasm and nucleus in a Ran GTPase-independent manner (PubMed:15654337).Recruits onto early endosomes in a Rab5- and HAP40-dependent fashion (PubMed:16476778). ... Of course, there is relevance to studying this section of the protein.

With the help of cryo-electron microscopy, the recently awarded Nobel Prize winning method, researchers have now decoded the three-dimensional, molecular structure of the healthy human huntingtin protein. Guo et al. Note: The mutant Huntingtin protein colocalizes with AKAP8L in the nuclear matrix of Huntington disease neurons. Here we report that selective autophagy requires an intact HTT protein in Drosophila and mouse CNS.
Since huntingtin is cleaved somewhere between residues 400 and 490, this section would hold relative importance in the intranuclear inclusions formed in Huntington's disease.

... molecular structure of the healthy human huntingtin protein. 613004 - HUNTINGTIN; HTT - IT15;; HD GENE - HTT Cryoelectron Microscopy. 3D Structure of Huntingtin Protein Decoded. 1.4.


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