View source for 7mpa


==Structure and topology of DWORF in bicelles by oriented solid-state NMR==
<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/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='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]
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== 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<ref>PMID:34875216</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7mpa" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Reddy UV]]
[[Category: Veglia GV]]
[[Category: Weber DK]]