HEATリピート

ヒートリピート
インポーチンβとインポーチンα IBBドメインの複合体の構造[1]
識別子
略号	HEAT
Pfam	PF03810
Pfam clan	CL0020
InterPro	IPR001494
SMART	SM000913
PROSITE	PS50166
SCOP	1QGK
SUPERFAMILY	1QGK
利用可能な蛋白質構造: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary PDB 1QGK

HEATリピート（ひーとりぴーと：HEAT repeats）は、多くのタンパク質に見られるリピート配列（構造）のひとつ[2]。ひとつのユニットは、30-40アミノ酸残基からなり、2本の両親媒性ヘリックスが折り畳まれた構造をつくる。このユニットが数十回繰り返されると、弾力性に富むソレノイド状構造を形成する[3][4][5]。

HEATリピートの名前の由来

HEATの名前は、このリピート配列を共有する代表的な4つのタンパク質の頭文字に由来する：Huntingtin (ハンチントン病の責任タンパク質ハンチンチン), Elongation factor 3 (EF3)（タンパク質合成伸長因子）, Protein phosphatase 2A (PP2A) A subunit（プロテインホスファターゼ2AのAサブユニット) , TOR1 (target of rapamycin)（シグナル伝達に関わるタンパク質キナーゼ）[6]。

様々なHEATタンパク質とその構造

HEATリピートタンパク質の代表例として知られているものには、核-細胞質間輸送因子インポーチンβ (karyopherin βとも呼ばれる) ファミリー[7]、コンデンシンやコヒーシンの制御サブユニット[8]、セパレース[9]、ATM (Ataxia telangiectasia mutated) やATR (Ataxia telangiectasia and Rad3 related)を含むPIKKs (phosphatidylinositol 3-kinase-related protein kinases)[10][11]、微小管結合タンパク質XMAP215/Dis1/TOG[12]とCLASP[13]などがある。このようにHEATリピートをもつタンパク質の細胞内機能は多彩である。

これまでに、構造が解かれているHEATリピートタンパク質には以下のものがある。

• タンパク質修飾・分解
  • PP2AのAサブユニット[14]とホロ酵素[15][16]
  • SCFユビキチンリガーゼ複合体の基質識別サブユニットとの複合体形成を阻害するCand1[17]
  • 26Sプロテアソームの分子集合に関わるシャペロンHsm3[18]

• 核-細胞質間輸送
  • インポーチンβ[1][19][20]
  • エクスポーチンCse1[21]
  • トランスポーチン１[22]
  • ヌクレオポリンGle1[23]; Nup188[24]; Nup192[25]

• 転写制御
  • 基本転写因子TFIIDのTAF6サブユニット[26]
  • TBP制御因子Mot1（Modifier of transcription 1）[27]
  • 転写開始因子Rrn3[28]

• 翻訳制御
  • 翻訳伸長因子eEF3[29]
  • 翻訳開始因子eIF4G[30]
  • アミノアシルtRNAの受け渡しを行うCex1p[31]

• DNA修復
  • DNA-PK (DNA-dependent protein kinase)[32][33][34]
  • ファンコーニ貧血原因タンパク質FANCF (FANCF)[35]
  • 損傷DNA結合活性を有するAlkD (Alkylpurin DNA glycosylase)[36]
  • PIKKsのコシャペロンとして働くTel2[37]

• 染色体制御
  • コヒーシンサブユニットSA2[38]/Scc3[39][40]
  • コヒーシンローディング因子Scc2[41][42]
  • コヒーシンローディング因子NIPBL/Mis4 + コヒーシンサブユニットSTAG1/Psm3[43][44]
  • コヒーシン動態制御因子Wapl[45][46]
  • コヒーシン動態制御因子Pds5[47][48][49]
  • コヒーシンローディング因子Scc2[41][42]
  • コヒーシン切断因子Separase[50][51][52]
  • コンデンシンサブユニットCAP-G/ycg1[53][54]
  • コンデンシンサブユニットCAP-D2/ycs4[55][56]

• 細胞骨格制御
  • 微小管結合タンパク質TOG[57][58]/Stu2[59]

• 細胞増殖制御
  • TOR (target of rapamycin)[60]

• その他
  • API5 (Apoptosis inhibitor 5)[61]
  • V型ATPaseのHサブユニット[62]
  • 全身性エリテマトーデスの免疫応答の自己抗原Ro[63]
  • 細胞質ポリアデニル複合体symplekin[64]
  • 癌抑制遺伝子Tsc1[65]
  • COP9シグナロソームのサブユニット7（CSN7）[66]
  • PI4キナーゼStt4複合体のサブユニットEFR3[67]
  • レンズ上皮由来増殖因子LEDGFのIBD (HIV-1 integrase binding domain)[68]

類似の構造をもつリピート配列

HEATリピートと類似の構造をもつリピート配列として、アルマジロリピート（Armadillo [ARM] repeat）[69]、やPUFリピート（Pumilio/fem-3 mRNA binding factor [PUF] repeat[70][71]）がある。

引用文献

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