User:Dzmitry Mukha/sandbox1
From Proteopedia
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=== Natural variants and isoforms === | === Natural variants and isoforms === | ||
| - | Few natural variants of hnRNP A1 were found. Substitution <scene name='70/701439/ | + | Few natural variants of hnRNP A1 were found. Substitution |
| + | <scene name='70/701439/Na_binding_1_n73/1'>N73S</scene> ([http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?type=rs&rs=6533 rs6533]) has unknown impact on the protein function. ALS20 carries two substitutions, D314N and N319S, in C-terminal region<ref>PMID 23455423</ref>. | ||
Isoforms identified for hnRNP A1 have deletions in disordered C-terminal regions (residues 203 – 307 and 252 – 303) and do to affect RNA-binding UP1<ref>PMID 15489334</ref>. | Isoforms identified for hnRNP A1 have deletions in disordered C-terminal regions (residues 203 – 307 and 252 – 303) and do to affect RNA-binding UP1<ref>PMID 15489334</ref>. | ||
Revision as of 22:19, 18 May 2015
Nucleic acid binding mechanism of hnRNP A1
hnRNP A1 (alternative gene names: ALS19, ALS20, HNRPA1, IBMPFD3, HNRPA1L3) is a member of A/B subfamily of heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). hnRNP A1 is involved in the packaging of premature mRNA into hnRNP particles and transport of poly(A) mRNA from the nucleus to the cytoplasm. hnRNP A1 has been characterized as a component of protein complexes bound to premature mRNA (hnRNP complexes). hnRNP A1 is one of the most abundant and best-characterized components of hnRNP complexes. Human hnRNP functions also in telomere length regulation and miRNA biogenesis. It may play a role in the replication of RNA viruses.
Contents |
Structure overview
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Binding mechanism
Conservative residues
Interaction between RRM domains
Two RRMs are interaction with one another via two Arg-Asp salt bridges. The interactions between domains of UP1 is quite weak, since the orientation of the two RRMs can be influenced by nucleic acid binding or by contacts with neighboring molecules in the crystal lattice.
In the solution structure of free UP1, the two Arg-Asp salt bridges are conserved at the interface between RRM1 and RRM2.
Protein-protein interactions
Medical implications
Structures
X-ray
Solution NMR
References
- ↑ Xu RM, Jokhan L, Cheng X, Mayeda A, Krainer AR. Crystal structure of human UP1, the domain of hnRNP A1 that contains two RNA-recognition motifs. Structure. 1997 Apr 15;5(4):559-70. PMID:9115444
- ↑ Vitali J, Ding J, Jiang J, Zhang Y, Krainer AR, Xu RM. Correlated alternative side chain conformations in the RNA-recognition motif of heterogeneous nuclear ribonucleoprotein A1. Nucleic Acids Res. 2002 Apr 1;30(7):1531-8. PMID:11917013
- ↑ Ding J, Hayashi MK, Zhang Y, Manche L, Krainer AR, Xu RM. Crystal structure of the two-RRM domain of hnRNP A1 (UP1) complexed with single-stranded telomeric DNA. Genes Dev. 1999 May 1;13(9):1102-15. PMID:10323862
- ↑ Myers JC, Moore SA, Shamoo Y. Structure-based incorporation of 6-methyl-8-(2-deoxy-beta-ribofuranosyl)isoxanthopteridine into the human telomeric repeat DNA as a probe for UP1 binding and destabilization of G-tetrad structures. J Biol Chem. 2003 Oct 24;278(43):42300-6. Epub 2003 Aug 6. PMID:12904298 doi:http://dx.doi.org/10.1074/jbc.M306147200
- ↑ Myers JC, Shamoo Y. Human UP1 as a model for understanding purine recognition in the family of proteins containing the RNA recognition motif (RRM). J Mol Biol. 2004 Sep 17;342(3):743-56. PMID:15342234 doi:10.1016/j.jmb.2004.07.029
- ↑ Barraud P, Allain FH. Solution structure of the two RNA recognition motifs of hnRNP A1 using segmental isotope labeling: how the relative orientation between RRMs influences the nucleic acid binding topology. J Biomol NMR. 2012 Dec 18. PMID:23247503 doi:http://dx.doi.org/10.1007/s10858-012-9696-4
- ↑ Kim HJ, Kim NC, Wang YD, Scarborough EA, Moore J, Diaz Z, MacLea KS, Freibaum B, Li S, Molliex A, Kanagaraj AP, Carter R, Boylan KB, Wojtas AM, Rademakers R, Pinkus JL, Greenberg SA, Trojanowski JQ, Traynor BJ, Smith BN, Topp S, Gkazi AS, Miller J, Shaw CE, Kottlors M, Kirschner J, Pestronk A, Li YR, Ford AF, Gitler AD, Benatar M, King OD, Kimonis VE, Ross ED, Weihl CC, Shorter J, Taylor JP. Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature. 2013 Mar 28;495(7442):467-73. doi: 10.1038/nature11922. Epub 2013 Mar 3. PMID:23455423 doi:http://dx.doi.org/10.1038/nature11922
- ↑ Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. PMID:15489334 doi:14/10b/2121
