2l9u

From Proteopedia

Spatial structure of dimeric ErbB3 transmembrane domain

Structural highlights

2l9u is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

ERBB3_HUMAN Defects in ERBB3 are the cause of lethal congenital contracture syndrome type 2 (LCCS2) [MIM:607598; also called Israeli Bedouin multiple contracture syndrome type A. LCCS2 is an autosomal recessive neurogenic form of a neonatally lethal arthrogryposis that is associated with atrophy of the anterior horn of the spinal cord. The LCCS2 syndrome is characterized by multiple joint contractures, anterior horn atrophy in the spinal cord, and a unique feature of a markedly distended urinary bladder. The phenotype suggests a spinal cord neuropathic etiology.^[1]

Function

ERBB3_HUMAN Binds and is activated by neuregulins and NTAK.^[2]

Publication Abstract from PubMed

In present work the interaction of two TM alpha-helices of the ErbB3 receptor tyrosine kinase from the ErbB or HER family (residues 639-670) was studied by means of NMR spectroscopy in a membrane-mimicking environment provided by the DPC micelles. The ErbB3 TM segment appeared to form a parallel symmetric dimer in a left-handed orientation. The interaction between TM spans is accomplished via the non-standard motif and is supported by apolar contacts of bulky side chains and by stacking of aromatic rings together with pi-cation interactions of Phe and Arg side chains. The investigation of the dimer--monomer equilibrium revealed thermodynamic properties of the assembly and the presence of two distinct regimes of the dimerization at low and at high peptide/detergent ratio. It was found that the detergent in case of ErbB3 behaves not as an ideal solvent, thus affecting the dimer--monomer equilibrium. Such behavior may account for the problems occurring with the refolding and stability of multispan helical membrane proteins in detergent solutions. The example of ErbB3 allows us to conclude that the thermodynamic parameters of dimerization, measured in micelles for two different helical pairs, cannot be compared without the investigation of their dependence on detergent concentration.

Spatial structure and dimer--monomer equilibrium of the ErbB3 transmembrane domain in DPC micelles.,Mineev KS, Khabibullina NF, Lyukmanova EN, Dolgikh DA, Kirpichnikov MP, Arseniev AS Biochim Biophys Acta. 2011 Aug;1808(8):2081-8. doi: 10.1016/j.bbamem.2011.04.017., Epub 2011 May 6. PMID:21575594^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Narkis G, Ofir R, Manor E, Landau D, Elbedour K, Birk OS. Lethal congenital contractural syndrome type 2 (LCCS2) is caused by a mutation in ERBB3 (Her3), a modulator of the phosphatidylinositol-3-kinase/Akt pathway. Am J Hum Genet. 2007 Sep;81(3):589-95. Epub 2007 Jul 24. PMID:17701904 doi:S0002-9297(07)61355-X
↑ Kinugasa Y, Ishiguro H, Tokita Y, Oohira A, Ohmoto H, Higashiyama S. Neuroglycan C, a novel member of the neuregulin family. Biochem Biophys Res Commun. 2004 Sep 3;321(4):1045-9. PMID:15358134 doi:10.1016/j.bbrc.2004.07.066
↑ Mineev KS, Khabibullina NF, Lyukmanova EN, Dolgikh DA, Kirpichnikov MP, Arseniev AS. Spatial structure and dimer--monomer equilibrium of the ErbB3 transmembrane domain in DPC micelles. Biochim Biophys Acta. 2011 Aug;1808(8):2081-8. doi: 10.1016/j.bbamem.2011.04.017., Epub 2011 May 6. PMID:21575594 doi:http://dx.doi.org/10.1016/j.bbamem.2011.04.017