2LCX

Spatial Structure of the ErbB4 dimeric TM domain

Summary for 2LCX

• Entry DOI: 10.2210/pdb2lcx/pdb
• NMR Information: BMRB: 7205
• Descriptor: Receptor tyrosine-protein kinase erbB-4 (1 entity in total)
• Functional Keywords: tranmsembrane, helical dimer, dimerization, her, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Single-pass type I membrane protein. ERBB4 intracellular domain: Nucleus: Q15303
• Total number of polymer chains: 2
• Total formula weight: 9539.66

Authors

Mineev, K.S.,Bocharov, E.V.,Arseniev, A.S. (deposition date: 2011-05-11, release date: 2012-05-16, Last modification date: 2024-05-15)

Primary citation

Bocharov, E.V.,Mineev, K.S.,Goncharuk, M.V.,Arseniev, A.S.
Structural and thermodynamic insight into the process of "weak" dimerization of the ErbB4 transmembrane domain by solution NMR.
Biochim.Biophys.Acta, 1818:2158-2170, 2012

PubMed Abstract: Specific helix-helix interactions between the single-span transmembrane domains of receptor tyrosine kinases are believed to be important for their lateral dimerization and signal transduction. Establishing structure-function relationships requires precise structural-dynamic information about this class of biologically significant bitopic membrane proteins. ErbB4 is a ubiquitously expressed member of the HER/ErbB family of growth factor receptor tyrosine kinases that is essential for the normal development of various adult and fetal human tissues and plays a role in the pathobiology of the organism. The dimerization of the ErbB4 transmembrane domain in membrane-mimicking lipid bicelles was investigated by solution NMR. In a bicellar DMPC/DHPC environment, the ErbB4 membrane-spanning α-helices (651-678)(2) form a right-handed parallel dimer through the N-terminal double GG4-like motif A(655)GxxGG(660) in a fashion that is believed to permit proper kinase domain activation. During helix association, the dimer subunits undergo a structural adjustment (slight bending) with the formation of a network of inter-monomeric polar contacts. The quantitative analysis of the observed monomer-dimer equilibrium provides insights into the kinetics and thermodynamics of the folding process of the helical transmembrane domain in the model environment that may be directly relevant to the process that occurs in biological membranes. The lipid bicelles occupied by a single ErbB4 transmembrane domain behave as a true ("ideal") solvent for the peptide, while multiply occupied bicelles are more similar to the ordered lipid microdomains of cellular membranes and appear to provide substantial entropic enhancement of the weak helix-helix interactions, which may be critical for membrane protein activity.

PubMed: 22579757
DOI: 10.1016/j.bbamem.2012.05.001

Experimental method

SOLUTION NMR