Ataxin 7

Ataxin-7 (ATXN7) is a protein of the SCA7 gene, located on chromosome 3. It is a subunit of the SAGA chromatin remodeling complex, which regulates gene expression; it contains 892 amino acids with an expandable poly(Q) region close to the N-terminus.^[1] The expandable poly(Q) motif region in the protein contributes crucially to spinocerebellar ataxia (SCA) pathogenesis by the induction of intranuclear inclusion bodies.^[2] ATXN7 is associated with both olivopontocerebellar atrophy type 3 (OPCA3) and spinocerebellar ataxia type 7 (SCA7).

Ataxin-7
Ataxin-7 is a protein within the SAGA chromatin remodeling complex. It acts as a transcription factor that regulates gene expression. The N-terminus is shown at the bottom.
Identifiers
Symbol	ATXN7
Alt. symbols	SCA7
NCBI gene	6314
HGNC	10560
OMIM	607640
PDB	7KTR
RefSeq	NM_000333
UniProt	O15265
Other data
Locus	Chr. 3 p21.1-p12
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SUPT20H
SUPT20H is a subunit of the SAGA coactivator complex that regulates gene expression. SPT20H holds ATXN7 down to the core of the complex.
Identifiers
Symbol	SUPT20H
Alt. symbols	SPT20H; bA421P11.4; P38IP
NCBI gene	110679609
HGNC	20596
PDB	7KTR
RefSeq	KAI4063086.1
UniProt	Q8NEM7-3
Other data
Locus	Chr. 3 q13.3
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SAGA Coactivator Complex
ATXN7 (yellow) and SPT20H (blue) in the large SAGA coactivator complex. SAGA has a size of 1.4-MDa and is a regulatory hub for gene expression, chromatin modification, and DNA damage repair and signaling.
Identifiers
Symbol	SAGA or STAGA
Alt. symbols	Spt-Ada-Gcn5 acetyltransferase
PDB	7KTR

Several CAG repeats within the coding region of the SCA genes will lead to pathological protein misfolding. The allele linked to SCA7 carries 37—306 CAG repeats near the N-terminus, whereas the normal allele has only 4—35 repeats.^[3] The CAG repeats in the ATXN7 gene have been linked to cerebellar and brainstem degeneration as well as retinal conerod dystrophy. The polyglutamine (polyQ) expansion at the N-terminus causes protein aggregation, impairing the gene expression of photoreceptor cell survival, leading to the symptoms of ataxia and vision loss.^[4] Research suggest that silencing of ATXN7 in the retina by RNAi can be a possible therapeutic strategy for patients with SCA7 retinal degeneration.^[5]

The N-terminus of ATXN7 is attached to a structural scaffold protein in the SAGA complex, SUPT20H.^[6] This interaction positions ATXN7 so that it can connect the deubiquitination (DUB) module to the complex, which is needed to remove ubiquitin modifications from histones, an essential step in transcription.^[6][7] Without the interaction between an arginine (Arg531) on ATXN7's N-terminus and a serine (Ser182) on the SUPT20H protein, the DUB module would not be anchored to the SAGA complex correctly, leading to defects in histone deubiquitination and gene regulation.^[6][7] Because of the length of the interaction being 3.3Å, it is characterized as a hydrogen bond keeping the two proteins attached.

SPT20H is able to keep ATXN7 attached to the core of the SAGA coactivator complex through this interaction between the Ser182 on SPT20H (blue) and the Arg531 on ATXN7 (yellow). This interaction can be characterized as a hydrogen bond.