POP5
Podjedinica POP5 ribonukleaze P/proteina MRP je enzim koji je kod ljudi kodiran genom POP5.[5][6]
U nedavnom radu navodi se da hipoplazija hrskavice i dlake (CHH) uzrokovana je mutacijama u genu koji kodira komponentu RNK RNaza MRP. Još nije poznato kako ove mutacije utiču na funkciju ove endoribonukleaze. Istraživan je učinak mutacija u P3 domenu na vezivanje proteina i nabiranje RNK. Dobijeni podaci pokazuju da su brojne supstitucije nukleotida P3 smanjile efikasnost njegove interakcije sa Rpp25 i Rpp20, dvije proteinske podjedinice koje se vezuju kao heterodimer za ovaj domen. Supstitucija 40G > A povezana sa CHH, kao i zamjena ostatka 47, gotovo je potpuno poništila vezivanje Rpp25 i Rpp20 u različitim testovima. Također, druge mutacije P3 povezane sa CHH smanjile su efikasnost kojom je RNaza MRP RNK vezana za Rpp25-Rpp20. Ovi podaci pokazuju da se najvažniji ostaci za vezivanje dimera Rpp25-Rpp20 nalaze u apikalnoj matičnoj petlji domena P3. Strukturne analize pomoću NMR-a nisu samo pokazale da ova petlja može usvojiti strukturu trostruke pseudopetlje, već su pokazale i da supstitucija 40G > A mijenja nabiranje ovog dijela domena P3. Tipodaci su prvi koji pružaju uvid u molekulski mehanizam kojim mutacije povezane s CHH utiču na funkciju RNaze MRP.[7]
Aminokiselinska sekvenca
[uredi | uredi izvor]Dužina polipeptidnog lanca je 163 aminokiseline, a molekulska težina 18.820 Da.[8]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MVRFKHRYLL | CELVSDDPRC | RLSLDDRVLS | SLVRDTIARV | HGTFGAAACS | ||||
| IGFAVRYLNA | YTGIVLLRCR | KEFYQLVWSA | LPFITYLENK | GHRYPCFFNT | ||||
| LHVGGTIRTC | QKFLIQYNRR | QLLILLQNCT | DEGEREAIQK | SVTRSCLLEE | ||||
| EEESGEEAAE | AME |
- Simboli
C: Cistein
D: Asparaginska kiselina
E: Glutaminska kiselina
F: Fenilalanin
G: Glicin
H: Histidin
I: Izoleucin
K: Lizin
L: Leucin
M: Metionin
N: Asparagin
P: Prolin
Q: Glutamin
R: Arginin
S: Serin
T: Treonin
V: Valin
W: Triptofan
Y: Tirozin
Reference
[uredi | uredi izvor]- ^ a b c GRCh38: Ensembl release 89: ENSG00000167272 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000060152 - 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.
- ^ van Eenennaam H, Lugtenberg D, Vogelzangs JH, van Venrooij WJ, Pruijn GJ (Aug 2001). "hPop5, a protein subunit of the human RNase MRP and RNase P endoribonucleases". J Biol Chem. 276 (34): 31635–41. doi:10.1074/jbc.M103399200. PMID 11413139.
- ^ "Entrez Gene: POP5 processing of precursor 5, ribonuclease P/MRP subunit (S. cerevisiae)".
- ^ Tim J M Welting , Sandy Mattijssen, Florence M A Peters, Nienke L van Doorn, Lianne Dekkers, Walther J van Venrooij, Hans A Heus, Luisa Bonafé, Ger J M Pruijn (2007): Cartilage-hair hypoplasia-associated mutations in the RNase MRP P3 domain affect RNA folding and ribonucleoprotein assembly. Biochim Biophys Acta, 1783(3):455-66.pmid: 18164267, doi: 10.1016/j.bbamcr.
- ^ "UniProt, Q969H6". Pristupljeno 12. 8. 2021.
Dopunska literatura
[uredi | uredi izvor]- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- van Eenennaam H, Pruijn GJ, van Venrooij WJ (1999). "hPop4: a new protein subunit of the human RNase MRP and RNase P ribonucleoprotein complexes". Nucleic Acids Res. 27 (12): 2465–72. doi:10.1093/nar/27.12.2465. PMC 148449. PMID 10352175.
- Hu RM, Han ZG, Song HD, et al. (2000). "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning". Proc. Natl. Acad. Sci. U.S.A. 97 (17): 9543–8. doi:10.1073/pnas.160270997. PMC 16901. PMID 10931946.
- Zhang QH, Ye M, Wu XY, et al. (2001). "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells". Genome Res. 10 (10): 1546–60. doi:10.1101/gr.140200. PMC 310934. PMID 11042152.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Welting TJ, van Venrooij WJ, Pruijn GJ (2004). "Mutual interactions between subunits of the human RNase MRP ribonucleoprotein complex". Nucleic Acids Res. 32 (7): 2138–46. doi:10.1093/nar/gkh539. PMC 407822. PMID 15096576.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
- Olsen JV, Blagoev B, Gnad F, et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983. S2CID 7827573.