4ZW2
Crystal structure of the Mouse voltage gated calcium channel beta subunit isoform 1a in complex with Alpha Interaction Domain peptide.
Summary for 4ZW2
| Entry DOI | 10.2210/pdb4zw2/pdb |
| Descriptor | Voltage-dependent L-type calcium channel subunit beta-1,Voltage-dependent L-type calcium channel subunit beta-1, Voltage-dependent L-type calcium channel subunit alpha-1S, TRIETHYLENE GLYCOL, ... (4 entities in total) |
| Functional Keywords | dihydropyridine receptor, cavbeta, excitation contraction coupling, alpha interacting domain, metal transport |
| Biological source | Mus musculus (Mouse) More |
| Cellular location | Cell membrane, sarcolemma ; Peripheral membrane protein ; Cytoplasmic side : Q8R3Z5 Cell membrane, sarcolemma ; Multi-pass membrane protein : Q02789 |
| Total number of polymer chains | 2 |
| Total formula weight | 40072.79 |
| Authors | Norris, N.C.,Oakley, A.J. (deposition date: 2015-05-19, release date: 2016-06-01, Last modification date: 2024-11-20) |
| Primary citation | Norris, N.C.,Joseph, S.,Aditya, S.,Karunasekara, Y.,Board, P.G.,Dulhunty, A.F.,Oakley, A.J.,Casarotto, M.G. Structural and biophysical analyses of the skeletal dihydropyridine receptor beta subunit beta 1a reveal critical roles of domain interactions for stability. J. Biol. Chem., 292:8401-8411, 2017 Cited by PubMed Abstract: Excitation-contraction (EC) coupling in skeletal muscle requires a physical interaction between the voltage-gated calcium channel dihydropyridine receptor (DHPR) and the ryanodine receptor Ca release channel. Although the exact molecular mechanism that initiates skeletal EC coupling is unresolved, it is clear that both the α and β subunits of DHPR are essential for this process. Here, we employed a series of techniques, including size-exclusion chromatography-multi-angle light scattering, differential scanning fluorimetry, and isothermal calorimetry, to characterize various biophysical properties of the skeletal DHPR β subunit β Removal of the intrinsically disordered N and C termini and the hook region of β prevented oligomerization, allowing for its structural determination by X-ray crystallography. The structure had a topology similar to that of previously determined β isoforms, which consist of SH3 and guanylate kinase domains. However, transition melting temperatures derived from the differential scanning fluorimetry experiments indicated a significant difference in stability of ∼2-3 °C between the β and β constructs, and the addition of the DHPR α I-II loop (α-interaction domain) peptide stabilized both β isoforms by ∼6-8 °C. Similar to other β isoforms, β bound with nanomolar affinity to the α-interaction domain, but binding affinities were influenced by amino acid substitutions in the adjacent SH3 domain. These results suggest that intramolecular interactions between the SH3 and guanylate kinase domains play a role in the stability of β while also providing a conduit for allosteric signaling events. PubMed: 28351836DOI: 10.1074/jbc.M116.763896 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.86 Å) |
Structure validation
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