7mpa

From Proteopedia

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