Premium
Quaternary architecture of PKA RIβ holoenzyme reveals isoform diversity (802.5)
Author(s) -
Ilouz Ronit,
Wu Jian,
Kornev Alexandr,
Taylor Susan,
Bubis José,
Blumenthal Donald
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.802.5
Subject(s) - tetramer , protein quaternary structure , gene isoform , protein subunit , small angle x ray scattering , chemistry , dimer , protein structure , crystallography , stereochemistry , biophysics , biochemistry , enzyme , biology , physics , scattering , gene , organic chemistry , optics
The cAMP‐dependent protein kinase A (PKA) holoenzyme is composed of two catalytic (C) subunits and a regulatory (R) subunit dimer. Although much is known about the structures and function of RIα, RIIα and RIIβ isoforms, little is known about RIβ. Given its unique biological importance and functional non‐redundancy, we hypothesized that RIβ will also have unique structural properties. We show first that the RIβ2:C2 overall quaternary structure is different from RIα2:C2, its closest homolog, using small angle x‐ray scattering (SAXS). We found that RIβ is more enriched in mouse mitochondria than RIα. We then obtained a crystal structure of the tetramer holoenzyme with the full‐length RIβ bound to the C‐subunit. This is the first PKA tetramer structure where all the domains can be visualized. The head‐to‐head alignment of the C‐subunits is in striking contrast to RIα where the C‐subunits do not contact each other. The structure allows us to appreciate how assembly of the R2:C2 complex creates isoform diversity even though the conformations of the R:C heterodimers are similar in all isoforms. Conserved tertiary structure does not translate into conserved quaternary structure. This structure paves the way for exploring the biological properties of RIβ.