3TE3

Coiled-coil oligomerization domain of the polycystin transient receptor potential channel PKD2L1

3TE3 の概要

• エントリーDOI: 10.2210/pdb3te3/pdb
• 分子名称: Polycystic kidney disease 2-like 1 protein (2 entities in total)
• 機能のキーワード: trimeric coiled-coil, oligomerization domain, c-terminal cytoplasmic regulatory domain, metal transport
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell projection, cilium membrane; Multi-pass membrane protein: Q9P0L9
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 25986.13

構造登録者

Yernool, D.A.,Molland, K.M. (登録日: 2011-08-11, 公開日: 2012-01-18, 最終更新日: 2024-02-28)

主引用文献

Molland, K.L.,Paul, L.N.,Yernool, D.A.
Crystal structure and characterization of coiled-coil domain of the transient receptor potential channel PKD2L1.
Biochim.Biophys.Acta, 1824:413-421, 2011

PubMed Abstract: The cation-permeable channel PKD2L1 forms a homomeric assembly as well as heteromeric associations with both PKD1 and PKD1L3, with the cytoplasmic regulatory domain (CRD) of PKD2L1 often playing a role in assembly and/or function. Our previous work indicated that the isolated PKD2L1 CRD assembles as a trimer in a manner dependent on the presence of a proposed oligomerization domain. Herein we describe the 2.7Å crystal structure of a segment containing the PKD2L1 oligomerization domain which indicates that trimerization is driven by the β-branched residues at the first and fourth positions of a heptad repeat (commonly referred to as "a" and "d") and by a conserved R-h-x-x-h-E salt bridge motif that is largely unique to parallel trimeric coiled coils. Further analysis of the PKD2L1 CRD indicates that trimeric association is sufficiently strong that no other species are present in solution in an analytical ultracentrifugation experiment at the lowest measurable concentration of 750nM. Conversely, mutation of the "a" and "d" residues leads to formation of an exclusively monomeric species, independent of concentration. Although both monomeric and WT CRDs are stable in solution and bind calcium with 0.9μM affinity, circular dichroism studies reveal that the monomer loses 25% more α-helical content than WT when stripped of this ligand, suggesting that the CRD structure is stabilized by trimerization in the ligand-free state. This stability could play a role in the function of the full-length complex, indicating that trimerization may be important for both homo- and possibly heteromeric assemblies of PKD2L1.

PubMed: 22193359
DOI: 10.1016/j.bbapap.2011.12.002

実験手法

X-RAY DIFFRACTION (2.694 Å)