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6d2z

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Revision as of 09:56, 18 December 2019

Structure of human Usb1 with uridine-adenosine, inactive H208Q mutant

Structural highlights

6d2z is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	USB1, C16orf57 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[USB1_HUMAN] Dyskeratosis congenita;Poikiloderma with neutropenia. Poikiloderma with neutropenia (PN) [MIM:604173]: A genodermatosis characterized by poikiloderma, pachyonychia and chronic neutropenia. The disorder starts as a papular erythematous rash on the limbs during the first year of life. It gradually spreads centripetally and, as the papular rash resolves, hypo- and hyperpigmentation result, with development of telangiectasias. Another skin manifestation is pachyonychia, but alopecia and leukoplakia are distinctively absent. Patients have recurrent pneumonias that usually result in reactive airway disease and/or chronic cough. One of the most important extracutaneous symptoms is an increased susceptibility to infections, mainly affecting the respiratory system, primarily due to a chronic neutropenia and to neutrophil functional defects. Bone marrow abnormalities account for neutropenia and may evolve into myelodysplasia associated with the risk of leukemic transformation. Poikiloderma with neutropenia shows phenotypic overlap with Rothmund-Thomson syndrome. Note=The disease is caused by mutations affecting the gene represented in this entry.^[1] ^[2]

Function

[USB1_HUMAN] Phosphodiesterase responsible for the U6 snRNA 3' end processing. Acts as an exoribonuclease (RNase) responsible for trimming the poly(U) tract of the last nucleotides in the pre-U6 snRNA molecule, leading to the formation of mature U6 snRNA 3' end-terminated with a 2',3'-cyclic phosphate.^[3] ^[4]

Publication Abstract from PubMed

Post-transcriptional modification of snRNA is central to spliceosome function. Usb1 is an exoribonuclease that shortens the oligo-uridine tail of U6 snRNA, resulting in a terminal 2',3' cyclic phosphate group in most eukaryotes, including humans. Loss of function mutations in human Usb1 cause the rare disorder poikiloderma with neutropenia (PN), and result in U6 snRNAs with elongated 3' ends that are aberrantly adenylated. Here, we show that human Usb1 removes 3' adenosines with 20-fold greater efficiency than uridines, which explains the presence of adenylated U6 snRNAs in cells lacking Usb1. We determined three high-resolution co-crystal structures of Usb1: wild-type Usb1 bound to the substrate analog adenosine 5'-monophosphate, and an inactive mutant bound to RNAs with a 3' terminal adenosine and uridine. These structures, along with QM/MM MD simulations of the catalytic mechanism, illuminate the molecular basis for preferential deadenylation of U6 snRNA. The extent of Usb1 processing is influenced by the secondary structure of U6 snRNA.

Structural and mechanistic basis for preferential deadenylation of U6 snRNA by Usb1.,Nomura Y, Roston D, Montemayor EJ, Cui Q, Butcher SE Nucleic Acids Res. 2018 Sep 12. pii: 5095463. doi: 10.1093/nar/gky812. PMID:30215753^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Volpi L, Roversi G, Colombo EA, Leijsten N, Concolino D, Calabria A, Mencarelli MA, Fimiani M, Macciardi F, Pfundt R, Schoenmakers EF, Larizza L. Targeted next-generation sequencing appoints c16orf57 as clericuzio-type poikiloderma with neutropenia gene. Am J Hum Genet. 2010 Jan;86(1):72-6. doi: 10.1016/j.ajhg.2009.11.014. Epub 2009, Dec 10. PMID:20004881 doi:10.1016/j.ajhg.2009.11.014
↑ Tanaka A, Morice-Picard F, Lacombe D, Nagy N, Hide M, Taieb A, McGrath J. Identification of a homozygous deletion mutation in C16orf57 in a family with Clericuzio-type poikiloderma with neutropenia. Am J Med Genet A. 2010 Jun;152A(6):1347-8. doi: 10.1002/ajmg.a.33455. PMID:20503306 doi:10.1002/ajmg.a.33455
↑ Mroczek S, Krwawicz J, Kutner J, Lazniewski M, Kucinski I, Ginalski K, Dziembowski A. C16orf57, a gene mutated in poikiloderma with neutropenia, encodes a putative phosphodiesterase responsible for the U6 snRNA 3' end modification. Genes Dev. 2012 Sep 1;26(17):1911-25. doi: 10.1101/gad.193169.112. Epub 2012 Aug , 16. PMID:22899009 doi:10.1101/gad.193169.112
↑ Hilcenko C, Simpson PJ, Finch AJ, Bowler FR, Churcher MJ, Jin L, Packman LC, Shlien A, Campbell P, Kirwan M, Dokal I, Warren AJ. Aberrant 3' oligoadenylation of spliceosomal U6 small nuclear RNA in poikiloderma with neutropenia. Blood. 2012 Nov 27. PMID:23190533 doi:10.1182/blood-2012-10-461491
↑ Nomura Y, Roston D, Montemayor EJ, Cui Q, Butcher SE. Structural and mechanistic basis for preferential deadenylation of U6 snRNA by Usb1. Nucleic Acids Res. 2018 Sep 12. pii: 5095463. doi: 10.1093/nar/gky812. PMID:30215753 doi:http://dx.doi.org/10.1093/nar/gky812

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6d2z"

@@ Line 1: / Line 1: @@
 ==Structure of human Usb1 with uridine-adenosine, inactive H208Q mutant==
-<StructureSection load='6d2z' size='340' side='right' caption='[[6d2z]], [[Resolution|resolution]] 1.18&Aring;' scene=''>
+<StructureSection load='6d2z' size='340' side='right'caption='[[6d2z]], [[Resolution|resolution]] 1.18&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[6d2z]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D2Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D2Z FirstGlance]. <br>
@@ Line 21: / Line 21: @@
 </div>
 <div class="pdbe-citations 6d2z" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
 == References ==
 <references/>
@@ Line 26: / Line 29: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Butcher, S E]]
 [[Category: Montemayor, E J]]

6d2z

From Proteopedia

Revision as of 09:56, 18 December 2019

Structure of human Usb1 with uridine-adenosine, inactive H208Q mutant

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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