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7mpa

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Structure and topology of DWORF in bicelles by oriented solid-state NMR

Structural highlights

7mpa is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DWORF_HUMAN Enhances the activity of ATP2A1/SERCA1 ATPase in sarcoplasmic reticulum by displacing ATP2A1/SERCA1 inhibitors, thereby acting as a key regulator of skeletal muscle activity. Does not directly stimulate SERCA pump activity. Enhances sarcoplasmic reticulum Ca(2+) uptake and myocyte contractility by displacing the SERCA inhibitory peptides sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN).[UniProtKB:P0DN83]

Publication Abstract from PubMed

SERCA is a P-type ATPase embedded in the sarcoplasmic reticulum and plays a central role in muscle relaxation. SERCA's function is regulated by single-pass membrane proteins called regulins. Unlike other regulins, dwarf open reading frame (DWORF) expressed in cardiac muscle has a unique activating effect. Here, we determine the structure and topology of DWORF in lipid bilayers using a combination of oriented sample solid-state NMR spectroscopy and replica-averaged orientationally restrained molecular dynamics. We found that DWORF's structural topology consists of a dynamic N-terminal domain, an amphipathic juxtamembrane helix that crosses the lipid groups at an angle of 64 degrees , and a transmembrane C-terminal helix with an angle of 32 degrees . A kink induced by Pro15, unique to DWORF, separates the two helical domains. A single Pro15Ala mutant significantly decreases the kink and eliminates DWORF's activating effect on SERCA. Overall, our findings directly link DWORF's structural topology to its activating effect on SERCA.

A kink in DWORF helical structure controls the activation of the sarcoplasmic reticulum Ca(2+)-ATPase.,Reddy UV, Weber DK, Wang S, Larsen EK, Gopinath T, De Simone A, Robia S, Veglia G Structure. 2021 Nov 27. pii: S0969-2126(21)00415-9. doi:, 10.1016/j.str.2021.11.003. PMID:34875216^[1]

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

References

↑ Reddy UV, Weber DK, Wang S, Larsen EK, Gopinath T, De Simone A, Robia S, Veglia G. A kink in DWORF helical structure controls the activation of the sarcoplasmic reticulum Ca(2+)-ATPase. Structure. 2021 Nov 27. pii: S0969-2126(21)00415-9. doi:, 10.1016/j.str.2021.11.003. PMID:34875216 doi:http://dx.doi.org/10.1016/j.str.2021.11.003

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7mpa"

Categories: Homo sapiens | Large Structures | Reddy UV | Veglia GV | Weber DK

@@ Line 1: / Line 1: @@
 ==Structure and topology of DWORF in bicelles by oriented solid-state NMR==
-<StructureSection load='7mpa' size='340' side='right'caption='[[7mpa]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
+<StructureSection load='7mpa' size='340' side='right'caption='[[7mpa]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7mpa]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MPA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MPA FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7mpa]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MPA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MPA FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">STRIT1, DWORF ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+</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=7mpa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mpa OCA], [https://pdbe.org/7mpa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mpa RCSB], [https://www.ebi.ac.uk/pdbsum/7mpa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mpa ProSAT]</span></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=7mpa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mpa OCA], [https://pdbe.org/7mpa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mpa RCSB], [https://www.ebi.ac.uk/pdbsum/7mpa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mpa ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/DWORF_HUMAN DWORF_HUMAN]] Enhances the activity of ATP2A1/SERCA1 ATPase in sarcoplasmic reticulum by displacing ATP2A1/SERCA1 inhibitors, thereby acting as a key regulator of skeletal muscle activity. Does not directly stimulate SERCA pump activity. Enhances sarcoplasmic reticulum Ca(2+) uptake and myocyte contractility by displacing the SERCA inhibitory peptides sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN).[UniProtKB:P0DN83]
+[https://www.uniprot.org/uniprot/DWORF_HUMAN DWORF_HUMAN] Enhances the activity of ATP2A1/SERCA1 ATPase in sarcoplasmic reticulum by displacing ATP2A1/SERCA1 inhibitors, thereby acting as a key regulator of skeletal muscle activity. Does not directly stimulate SERCA pump activity. Enhances sarcoplasmic reticulum Ca(2+) uptake and myocyte contractility by displacing the SERCA inhibitory peptides sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN).[UniProtKB:P0DN83]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 21: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Reddy, U V]]
+[[Category: Reddy UV]]
-[[Category: Veglia, G V]]
+[[Category: Veglia GV]]
-[[Category: Weber, D K]]
+[[Category: Weber DK]]
-[[Category: Chemical shift anisotropy]]
-[[Category: Dipolar coupling]]
-[[Category: Membrane protein]]
-[[Category: Miniprotein]]
-[[Category: Oriented solid state nmr spectroscopy]]
-[[Category: Regulin]]
-[[Category: Sarcoplasmic reticulum]]
-[[Category: Separated local field]]

7mpa

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Current revision

Structure and topology of DWORF in bicelles by oriented solid-state NMR

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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