XPB
XPB (xeroderma pigmentosum tip B) je ATP-ovisna DNK helikaza , kod ljudi koji je dio kompleksa transkripcijskog faktora TFIIH, Kod ljudi, gen XPB nalazi se na hromosomu 2.
Struktura
urediDr. John Tainer i njegova grupa u The Scripps Research Institute riješili su 3D strukturu arhejskog homologa XPB rendgenskom kristalografijom.[5]
Aminokiselinska sekvenca
urediDužina polipeptidnog lanca je 782 aminokiseline, a molekulska težina 89.278 Da.[5]
10 | 20 | 30 | 40 | 50 | ||||
---|---|---|---|---|---|---|---|---|
MGKRDRADRD | KKKSRKRHYE | DEEDDEEDAP | GNDPQEAVPS | AAGKQVDESG | ||||
TKVDEYGAKD | YRLQMPLKDD | HTSRPLWVAP | DGHIFLEAFS | PVYKYAQDFL | ||||
VAIAEPVCRP | THVHEYKLTA | YSLYAAVSVG | LQTSDITEYL | RKLSKTGVPD | ||||
GIMQFIKLCT | VSYGKVKLVL | KHNRYFVESC | HPDVIQHLLQ | DPVIRECRLR | ||||
NSEGEATELI | TETFTSKSAI | SKTAESSGGP | STSRVTDPQG | KSDIPMDLFD | ||||
FYEQMDKDEE | EEEETQTVSF | EVKQEMIEEL | QKRCIHLEYP | LLAEYDFRND | ||||
SVNPDINIDL | KPTAVLRPYQ | EKSLRKMFGN | GRARSGVIVL | PCGAGKSLVG | ||||
VTAACTVRKR | CLVLGNSAVS | VEQWKAQFKM | WSTIDDSQIC | RFTSDAKDKP | ||||
IGCSVAISTY | SMLGHTTKRS | WEAERVMEWL | KTQEWGLMIL | DEVHTIPAKM | ||||
FRRVLTIVQA | HCKLGLTATL | VREDDKIVDL | NFLIGPKLYE | ANWMELQNNG | ||||
YIAKVQCAEV | WCPMSPEFYR | EYVAIKTKKR | ILLYTMNPNK | FRACQFLIKF | ||||
HERRNDKIIV | FADNVFALKE | YAIRLNKPYI | YGPTSQGERM | QILQNFKHNP | ||||
KINTIFISKV | GDTSFDLPEA | NVLIQISSHG | GSRRQEAQRL | GRVLRAKKGM | ||||
VAEEYNAFFY | SLVSQDTQEM | AYSTKRQRFL | VDQGYSFKVI | TKLAGMEEED | ||||
LAFSTKEEQQ | QLLQKVLAAT | DLDAEEEVVA | GEFGSRSSQA | SRRFGTMSSM | ||||
SGADDTVYME | YHSSRSKAPS | KHVHPLFKRF | RK |
Funkcija
urediXPB ima značajnu ulogu u normalnoj baznoj transkripciji, transkripcijski spojenom popravku (TCR) i popravak ekscizijom nukleotida (NER). Pokazalo se da pročišćeni XPB odmotava DNK sa 3’-5’ polarnosti.
Funkcija XPB(ERCC3) proteina u NER-u je da pomogne u odmotavanju DNK dvostruke spirale nakon što se oštećenje prvobitno prepozna. NER je put u više koraka koji uklanja širok spektar različitih oštećenja DNK koja narušavaju normalno uparivanje baza. Takva oštećenja uključuju glomazne hemijske adukte, UV-inducirane pirimidinske dimere i nekoliko oblika oksidativnog oštećenja. Mutacije gena XPB(ERCC3) mogu kod ljudi dovesti do bolesti xeroderma pigmentosum (XP) ili XP u kombinaciji sa Cockayneovim sindromom (XPCS).[6] Mutantne XPB ćelije pojedinaca sa XPCS fenotipom su osjetljive na UV-zračenje i akutni oksidativni stres.[7]
Poremećaji
urediMutacije u XPB i drugim srodnim komplementarnim grupama, XPA-XPG, dovode do brojnih genetički poremećaj|genetičkih poremećaja]] kao što su Xeroderma pigmentosum, Cockayneov sindrom i trihotiodistrofija.
Interakcije
urediPokazalo se da je XPB u interakciji sa:
Inhibitori malih molekula
urediSnažni, bioaktivni prirodni proizvodi poput triptolida koji inhibiraju transkripciju sisara putem inhibicije XPB podjedinice općeg transkripcijskog faktora TFIIH nedavno su prijavljeni kao konjugat glukoze za ciljanje hipoksijskih ćelija raka s povećanom ekspresijom transportera glukoze.[18]
Također pogledajte
uredi- Xeroderma pigmentosum, komplementarna grupa G
Reference
uredi- ^ a b c GRCh38: Ensembl release 89: ENSG00000163161 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024382 - Ensembl, maj 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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- ^ Iyer N, Reagan MS, Wu KJ, Canagarajah B, Friedberg EC (februar 1996). "Interactions involving the human RNA polymerase II transcription/nucleotide excision repair complex TFIIH, the nucleotide excision repair protein XPG, and Cockayne syndrome group B (CSB) protein". Biochemistry. 35 (7): 2157–67. doi:10.1021/bi9524124. PMID 8652557.
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- ^ Yokoi M, Masutani C, Maekawa T, Sugasawa K, Ohkuma Y, Hanaoka F (mart 2000). "The xeroderma pigmentosum group C protein complex XPC-HR23B plays an important role in the recruitment of transcription factor IIH to damaged DNA". J. Biol. Chem. 275 (13): 9870–5. doi:10.1074/jbc.275.13.9870. PMID 10734143.
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Vanjski linkovi
uredi- GeneReviews/NIH/NCBI/UW entry on Xeroderma Pigmentosum
- XPBC-ERCC-3 protein na US National Library of Medicine Medical Subject Headings (MeSH)