| Structural highlights
Disease
[RM03_HUMAN] Combined oxidative phosphorylation defect type 9. The disease is caused by mutations affecting the gene represented in this entry. [RM44_HUMAN] Infantile hypertrophic cardiomyopathy due to MRPL44 deficiency. The disease is caused by mutations affecting the gene represented in this entry.
Function
[RM14_HUMAN] Forms part of 2 intersubunit bridges in the assembled ribosome. Upon binding to MALSU1 intersubunit bridge formation is blocked, preventing ribosome formation and repressing translation (Probable).[1] [G45IP_HUMAN] Acts as a negative regulator of G1 to S cell cycle phase progression by inhibiting cyclin-dependent kinases. Inhibitory effects are additive with GADD45 proteins but occurs also in the absence of GADD45 proteins. Acts as a repressor of the orphan nuclear receptor NR4A1 by inhibiting AB domain-mediated transcriptional activity. May be involved in the hormone-mediated regulation of NR4A1 transcriptional activity. May play a role in mitochondrial protein synthesis. [RM36_HUMAN] Component of the large subunit of the mitochondrial ribosome. [RM16_HUMAN] Component of the large subunit of mitochondrial ribosome. [ICT1_HUMAN] Essential peptidyl-tRNA hydrolase component of the mitochondrial large ribosomal subunit. Acts as a codon-independent translation release factor that has lost all stop codon specificity and directs the termination of translation in mitochondrion, possibly in case of abortive elongation. May be involved in the hydrolysis of peptidyl-tRNAs that have been prematurely terminated and thus in the recycling of stalled mitochondrial ribosomes.[2] [RM41_HUMAN] Component of the mitochondrial ribosome large subunit. Also involved in apoptosis and cell cycle. Enhances p53/TP53 stability, thereby contributing to p53/TP53-induced apoptosis in response to growth-inhibitory condition. Enhances p53/TP53 translocation to the mitochondria. Has the ability to arrest the cell cycle at the G1 phase, possibly by stabilizing the CDKN1A and CDKN1B (p27Kip1) proteins.[3] [4] [RM44_HUMAN] Component of the 39S subunit of mitochondrial ribosome. May have a function in the assembly/stability of nascent mitochondrial polypeptides exiting the ribosome.[5]
Publication Abstract from PubMed
Human mitochondrial ribosomes are highly divergent from all other known ribosomes and are specialized to exclusively translate membrane proteins. They are linked with hereditary mitochondrial diseases and are often the unintended targets of various clinically useful antibiotics. Using single-particle electron cryomicroscopy, we have determined the structure of its large subunit to 3.4 angstrom resolution, revealing 48 proteins, 21 of which are specific to mitochondria. The structure unveils an adaptation of the exit tunnel for hydrophobic nascent peptides, extensive remodeling of the central protuberance, including recruitment of mitochondrial tRNAVal to play an integral structural role, and changes in the tRNA binding sites related to the unusual characteristics of mitochondrial tRNAs.
Structure of the large ribosomal subunit from human mitochondria.,Brown A, Amunts A, Bai XC, Sugimoto Y, Edwards PC, Murshudov G, Scheres SH, Ramakrishnan V Science. 2014 Oct 2. pii: 1258026. PMID:25278503[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hauser R, Pech M, Kijek J, Yamamoto H, Titz B, Naeve F, Tovchigrechko A, Yamamoto K, Szaflarski W, Takeuchi N, Stellberger T, Diefenbacher ME, Nierhaus KH, Uetz P. RsfA (YbeB) proteins are conserved ribosomal silencing factors. PLoS Genet. 2012;8(7):e1002815. doi: 10.1371/journal.pgen.1002815. Epub 2012 Jul , 19. PMID:22829778 doi:10.1371/journal.pgen.1002815
- ↑ Richter R, Rorbach J, Pajak A, Smith PM, Wessels HJ, Huynen MA, Smeitink JA, Lightowlers RN, Chrzanowska-Lightowlers ZM. A functional peptidyl-tRNA hydrolase, ICT1, has been recruited into the human mitochondrial ribosome. EMBO J. 2010 Mar 17;29(6):1116-25. doi: 10.1038/emboj.2010.14. Epub 2010 Feb 25. PMID:20186120 doi:http://dx.doi.org/10.1038/emboj.2010.14
- ↑ Yoo YA, Kim MJ, Park JK, Chung YM, Lee JH, Chi SG, Kim JS, Yoo YD. Mitochondrial ribosomal protein L41 suppresses cell growth in association with p53 and p27Kip1. Mol Cell Biol. 2005 Aug;25(15):6603-16. PMID:16024796 doi:http://dx.doi.org/25/15/6603
- ↑ Kim MJ, Yoo YA, Kim HJ, Kang S, Kim YG, Kim JS, Yoo YD. Mitochondrial ribosomal protein L41 mediates serum starvation-induced cell-cycle arrest through an increase of p21(WAF1/CIP1). Biochem Biophys Res Commun. 2005 Dec 16;338(2):1179-84. Epub 2005 Oct 21. PMID:16256947 doi:http://dx.doi.org/10.1016/j.bbrc.2005.10.064
- ↑ Carroll CJ, Isohanni P, Poyhonen R, Euro L, Richter U, Brilhante V, Gotz A, Lahtinen T, Paetau A, Pihko H, Battersby BJ, Tyynismaa H, Suomalainen A. Whole-exome sequencing identifies a mutation in the mitochondrial ribosome protein MRPL44 to underlie mitochondrial infantile cardiomyopathy. J Med Genet. 2013 Mar;50(3):151-9. doi: 10.1136/jmedgenet-2012-101375. Epub 2013 , Jan 12. PMID:23315540 doi:http://dx.doi.org/10.1136/jmedgenet-2012-101375
- ↑ Brown A, Amunts A, Bai XC, Sugimoto Y, Edwards PC, Murshudov G, Scheres SH, Ramakrishnan V. Structure of the large ribosomal subunit from human mitochondria. Science. 2014 Oct 2. pii: 1258026. PMID:25278503 doi:http://dx.doi.org/10.1126/science.1258026
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