5LUM

Alpha-crystallin domain of human HSPB6 patched with its N-terminal peptide

Summary for 5LUM

• Entry DOI: 10.2210/pdb5lum/pdb
• Descriptor: Heat shock protein beta-6, SULFATE ION, ... (4 entities in total)
• Functional Keywords: protein-peptide complex, idrs, chaperone protein, protein/peptide
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm : O14558 O14558
• Total number of polymer chains: 10
• Total formula weight: 48197.98

Authors

Sluchanko, N.N.,Beelen, S.,Kulikova, A.A.,Weeks, S.D.,Antson, A.A.,Gusev, N.B.,Strelkov, S.V. (deposition date: 2016-09-09, release date: 2017-02-01, Last modification date: 2024-01-17)

Primary citation

Sluchanko, N.N.,Beelen, S.,Kulikova, A.A.,Weeks, S.D.,Antson, A.A.,Gusev, N.B.,Strelkov, S.V.
Structural Basis for the Interaction of a Human Small Heat Shock Protein with the 14-3-3 Universal Signaling Regulator.
Structure, 25:305-316, 2017

PubMed Abstract: By interacting with hundreds of protein partners, 14-3-3 proteins coordinate vital cellular processes. Phosphorylation of the small heat shock protein, HSPB6, within its intrinsically disordered N-terminal domain activates its interaction with 14-3-3, ultimately triggering smooth muscle relaxation. After analyzing the binding of an HSPB6-derived phosphopeptide to 14-3-3 using isothermal calorimetry and X-ray crystallography, we have determined the crystal structure of the complete assembly consisting of the 14-3-3 dimer and full-length HSPB6 dimer and further characterized this complex in solution using fluorescence spectroscopy, small-angle X-ray scattering, and limited proteolysis. We show that selected intrinsically disordered regions of HSPB6 are transformed into well-defined conformations upon the interaction, whereby an unexpectedly asymmetric structure is formed. This structure provides the first atomic resolution snapshot of a human small HSP in functional state, explains how 14-3-3 proteins sequester their regulatory partners, and can inform the design of small-molecule interaction modifiers to be used as myorelaxants.

PubMed: 28089448
DOI: 10.1016/j.str.2016.12.005

Experimental method

X-RAY DIFFRACTION (2.6 Å)