OCA at 10:22, 10 January 2024

OCA — Wed, 10 Jan 2024 10:22:18 GMT

←Older revision		Revision as of 10:22, 10 January 2024
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-	'''Unreleased structure'''

-	~~The entry~~ 8g5k is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Cryo-EM structure of the Wedge Alignment Complex (VIII) of Human Mitochondrial DNA Polymerase Gamma==
		+	<StructureSection load='8g5k' size='340' side='right'caption='[[8g5k]], [[Resolution\|resolution]] 2.90Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8g5k]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8G5K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8G5K FirstGlance]. <br>
		+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 2.9Å</td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8g5k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8g5k OCA], [https://pdbe.org/8g5k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8g5k RCSB], [https://www.ebi.ac.uk/pdbsum/8g5k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8g5k ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/DPOG1_HUMAN DPOG1_HUMAN] Defects in POLG are the cause of progressive external ophthalmoplegia with mitochondrial DNA deletions autosomal dominant type 1 (PEOA1) [MIM:[https://omim.org/entry/157640 157640]. Progressive external ophthalmoplegia is characterized by progressive weakness of ocular muscles and levator muscle of the upper eyelid. In a minority of cases, it is associated with skeletal myopathy, which predominantly involves axial or proximal muscles and which causes abnormal fatigability and even permanent muscle weakness. Ragged-red fibers and atrophy are found on muscle biopsy. A large proportion of chronic ophthalmoplegias are associated with other symptoms, leading to a multisystemic pattern of this disease. Additional symptoms are variable, and may include cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism.<ref>PMID:12210792</ref> <ref>PMID:11897778</ref> <ref>PMID:15534189</ref> <ref>PMID:15351195</ref> <ref>PMID:17420318</ref> <ref>PMID:18575922</ref> Defects in POLG are a cause of progressive external ophthalmoplegia with mitochondrial DNA deletions autosomal recessive (PEOB) [MIM:[https://omim.org/entry/258450 258450]. PEOB is a severe form of progressive external ophthalmoplegia. It is clinically more heterogeneous than the autosomal dominant forms. Can be more severe.<ref>PMID:15351195</ref> <ref>PMID:11431686</ref> <ref>PMID:12975295</ref> <ref>PMID:12872260</ref> <ref>PMID:14635118</ref> <ref>PMID:12707443</ref> <ref>PMID:12565911</ref> <ref>PMID:15349879</ref> <ref>PMID:15477547</ref> <ref>PMID:15917273</ref> <ref>PMID:16634032</ref> <ref>PMID:16401742</ref> <ref>PMID:16621917</ref> <ref>PMID:16639411</ref> Defects in POLG are a cause of sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO) [MIM:[https://omim.org/entry/607459 607459]. SANDO is a systemic disorder resulting from mitochondrial dysfunction associated with mitochondrial depletion in skeletal muscle and peripheral nerve tissue. The clinical triad of symptoms consists of sensory ataxic neuropathy, dysarthria, and ophthalmoparesis. However, the phenotype varies widely, even within the same family, and can also include myopathy, seizures, and hearing loss. An atypical form of the disease is characterized by headaches and/or seizures manifesting in childhood or adolescence, followed by development of cerebellar and sensory ataxia, dysarthria, progressive external ophthalmoplegia, and myoclonus in early adulthood.<ref>PMID:12565911</ref> <ref>PMID:15477547</ref> <ref>PMID:15917273</ref> <ref>PMID:16621917</ref> <ref>PMID:16639411</ref> <ref>PMID:14745080</ref> <ref>PMID:16080118</ref> <ref>PMID:15824347</ref> <ref>PMID:16919951</ref> Defects in POLG are the cause of mitochondrial DNA depletion syndrome type 4A (MTDPS4A) [MIM:[https://omim.org/entry/203700 203700]; also called Alpers diffuse degeneration of cerebral gray matter with hepatic cirrhosis. An autosomal recessive hepatocerebral syndrome. The typical course of the disease includes severe developmental delay, intractable seizures, liver failure, and death in childhood. Refractory seizures, cortical blindness, progressive liver dysfunction, and acute liver failure after exposure to valproic acid are considered diagnostic features. The neuropathological hallmarks are neuronal loss, spongiform degeneration, and astrocytosis of the visual cortex. Liver biopsy results show steatosis, often progressing to cirrhosis.<ref>PMID:16621917</ref> <ref>PMID:16639411</ref> <ref>PMID:15122711</ref> <ref>PMID:15929042</ref> <ref>PMID:15689359</ref> <ref>PMID:18828154</ref> Defects in POLG are the cause of mitochondrial DNA depletion syndrome type 4B (MTDPS4B) [MIM:[https://omim.org/entry/613662 613662]; also known as mitochondrial DNA depletion syndrome 4B MNGIE type or mitochondrial neurogastrointestinal encephalopathy syndrome POLG-related. An autosomal recessive progressive multisystem disorder clinically characterized by chronic gastrointestinal dysmotility and pseudo-obstruction, cachexia, progressive external ophthalmoplegia, axonal sensory ataxic neuropathy, and muscle weakness. Defects in POLG are a cause of Leigh syndrome (LS) [MIM:[https://omim.org/entry/256000 256000]. LS is a severe neurological disorder characterized by bilaterally symmetrical necrotic lesions in subcortical brain regions.<ref>PMID:18828154</ref>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/DPOG1_HUMAN DPOG1_HUMAN] Involved in the replication of mitochondrial DNA. Associates with mitochondrial DNA.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	DNA polymerase (DNAP) can correct errors in DNA during replication by proofreading, a process critical for cell viability. However, the mechanism by which an erroneously incorporated base translocates from the polymerase to the exonuclease site and the corrected DNA terminus returns has remained elusive. Here, we present an ensemble of nine high-resolution structures representing human mitochondrial DNA polymerase Gamma, Polgamma, captured during consecutive proofreading steps. The structures reveal key events, including mismatched base recognition, its dissociation from the polymerase site, forward translocation of DNAP, alterations in DNA trajectory, repositioning and refolding of elements for primer separation, DNAP backtracking, and displacement of the mismatched base into the exonuclease site. Altogether, our findings suggest a conserved 'bolt-action' mechanism of proofreading based on iterative cycles of DNAP translocation without dissociation from the DNA, facilitating primer transfer between catalytic sites. Functional assays and mutagenesis corroborate this mechanism, connecting pathogenic mutations to crucial structural elements in proofreading steps.

-	~~Authors~~:	+	Structural basis for DNA proofreading.,Buchel G, Nayak AR, Herbine K, Sarfallah A, Sokolova VO, Zamudio-Ochoa A, Temiakov D Nat Commun. 2023 Dec 27;14(1):8501. doi: 10.1038/s41467-023-44198-8. PMID:38151585<ref>PMID:38151585</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 8g5k" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Synthetic construct]]
		+	[[Category: Buchel G]]
		+	[[Category: Herbine KH]]
		+	[[Category: Nayak AR]]
		+	[[Category: Sarfallah A]]
		+	[[Category: Sokolova VO]]
		+	[[Category: Temiakov D]]
		+	[[Category: Zamudio-Ochoa A]]

OCA at 11:48, 20 September 2023

OCA — Wed, 20 Sep 2023 11:48:28 GMT

←Older revision		Revision as of 11:48, 20 September 2023
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8g5k is ON HOLD	+	The entry 8g5k is ON HOLD until Paper Publication

	Authors:		Authors:

OCA at 08:50, 2 August 2023

OCA — Wed, 02 Aug 2023 08:50:12 GMT

←Older revision		Revision as of 08:50, 2 August 2023
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8g5k is ON HOLD ~~until Paper Publication~~	+	The entry 8g5k is ON HOLD

	Authors:		Authors:

OCA at 03:51, 5 July 2023

OCA — Wed, 05 Jul 2023 03:51:34 GMT

←Older revision		Revision as of 03:51, 5 July 2023
Line 3:		Line 3:
	The entry 8g5k is ON HOLD until Paper Publication		The entry 8g5k is ON HOLD until Paper Publication

-	Authors: ~~Nayak, A.R., Buchel, G., Herbine, K.H., Sarfallah, A., Sokolova, V.O., Zamudio-Ochoa, A., Temiakov, D.~~	+	Authors:

-	Description: ~~Cryo-EM structure of the Wedge Alignment Complex (VII) of Human Mitochondrial DNA Polymerase Gamma~~	+	Description:
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Temiakov, D]]
-	[[Category: Herbine, K.H]]
-	[[Category: Zamudio-Ochoa, A]]
-	[[Category: Buchel, G]]
-	[[Category: Nayak, A.R]]
-	[[Category: Sokolova, V.O]]
-	[[Category: Sarfallah, A]]

OCA at 05:38, 22 March 2023

OCA — Wed, 22 Mar 2023 05:38:50 GMT

←Older revision		Revision as of 05:38, 22 March 2023
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8g5k is ON HOLD	+	The entry 8g5k is ON HOLD until Paper Publication

	Authors: Nayak, A.R., Buchel, G., Herbine, K.H., Sarfallah, A., Sokolova, V.O., Zamudio-Ochoa, A., Temiakov, D.		Authors: Nayak, A.R., Buchel, G., Herbine, K.H., Sarfallah, A., Sokolova, V.O., Zamudio-Ochoa, A., Temiakov, D.
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	Description: Cryo-EM structure of the Wedge Alignment Complex (VII) of Human Mitochondrial DNA Polymerase Gamma		Description: Cryo-EM structure of the Wedge Alignment Complex (VII) of Human Mitochondrial DNA Polymerase Gamma
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
		+	[[Category: Temiakov, D]]
	[[Category: Herbine, K.H]]		[[Category: Herbine, K.H]]
	[[Category: Zamudio-Ochoa, A]]		[[Category: Zamudio-Ochoa, A]]
-	[[Category: Temiakov, D]]
	[[Category: Buchel, G]]		[[Category: Buchel, G]]
	[[Category: Nayak, A.R]]		[[Category: Nayak, A.R]]
	[[Category: Sokolova, V.O]]		[[Category: Sokolova, V.O]]
	[[Category: Sarfallah, A]]		[[Category: Sarfallah, A]]

OCA: Protected "8g5k" [edit=sysop:move=sysop]

OCA — Wed, 22 Feb 2023 10:21:07 GMT

Protected "8g5k" [edit=sysop:move=sysop]

←Older revision

Revision as of 10:21, 22 February 2023

OCA: New page: '''Unreleased structure''' The entry 8g5k is ON HOLD Authors: Nayak, A.R., Buchel, G., Herbine, K.H., Sarfallah, A., Sokolova, V.O., Zamudio-Ochoa, A., Temiakov, D. Description: Cryo-E...

OCA — Wed, 22 Feb 2023 10:21:04 GMT

New page: '''Unreleased structure''' The entry 8g5k is ON HOLD Authors: Nayak, A.R., Buchel, G., Herbine, K.H., Sarfallah, A., Sokolova, V.O., Zamudio-Ochoa, A., Temiakov, D. Description: Cryo-E...

New page

'''Unreleased structure'''

The entry 8g5k is ON HOLD

Authors: Nayak, A.R., Buchel, G., Herbine, K.H., Sarfallah, A., Sokolova, V.O., Zamudio-Ochoa, A., Temiakov, D.

Description: Cryo-EM structure of the Wedge Alignment Complex (VII) of Human Mitochondrial DNA Polymerase Gamma
[[Category: Unreleased Structures]]
[[Category: Herbine, K.H]]
[[Category: Zamudio-Ochoa, A]]
[[Category: Temiakov, D]]
[[Category: Buchel, G]]
[[Category: Nayak, A.R]]
[[Category: Sokolova, V.O]]
[[Category: Sarfallah, A]]