geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Hydrophobic Mismatch Drives the Interaction of E5 with the Transmembrane Segment of PDGF Receptor


, : Hydrophobic Mismatch Drives the Interaction of E5 with the Transmembrane Segment of PDGF Receptor. Biophysical Journal 109(4): 737-749

The oncogenic E5 protein from bovine papillomavirus is a short (44 amino acids long) integral membrane protein that forms homodimers. It activates platelet-derived growth factor receptor (PDGFR) β in a ligand-independent manner by transmembrane helix-helix interactions. The nature of this recognition event remains elusive, as numerous mutations are tolerated in the E5 transmembrane segment, with the exception of one hydrogen-bonding residue. Here, we examined the conformation, stability, and alignment of the E5 protein in fluid lipid membranes of substantially varying bilayer thickness, in both the absence and presence of the PDGFR transmembrane segment. Quantitative synchrotron radiation circular dichroism analysis revealed a very long transmembrane helix for E5 of ∼26 amino acids. Oriented circular dichroism and solid-state (15)N-NMR showed that the alignment and stability of this unusually long segment depend critically on the membrane thickness. When reconstituted alone in exceptionally thick DNPC lipid bilayers, the E5 helix was found to be inserted almost upright. In moderately thick bilayers (DErPC and DEiPC), it started to tilt and became slightly deformed, and finally it became aggregated in conventional DOPC, POPC, and DMPC membranes due to hydrophobic mismatch. On the other hand, when E5 was co-reconstituted with the transmembrane segment of PDGFR, it was able to tolerate even the most pronounced mismatch and was stabilized by binding to the receptor, which has the same hydrophobic length. As E5 is known to activate PDGFR within the thin membranes of the Golgi compartment, we suggest that the intrinsic hydrophobic mismatch of these two interaction partners drives them together. They seem to recognize each other by forming a closely packed bundle of mutually aligned transmembrane helices, which is further stabilized by a specific pair of hydrogen-bonding residues.

US$19.90

PMID: 26287626

DOI: 10.1016/j.bpj.2015.07.022


Other references

Öberg, F.; Askenfelt, A., 2012: Acoustical and perceptual influence of duplex stringing in grand pianos. This study investigates the acoustical and perceptual influence of the string parts outside the speaking length in grand pianos (front and rear duplex strings). Acoustical measurements on a grand piano in concert condition were conducted, measurin...

Falls, J.H.; Barnacascel, W.R.; Britt, P.W., 1976: Direct potentiometric titration of urea with urease. AOAC method 2.070-2.071 for determining urea in N fertilizers with urease has given varying results according to the analyst's interpretation of titrating to a neutral end point. The method has been modified to allow the end point of the titr...

Wrba H.; Kokron O.; Titscher R., 1976: Ifosfamide in the treatment of lung cancer and metastases of solid malignant tumors. Hellmann, K And T A Connors (Ed ) Chemotherapy, Vol 8 Cancer Chemotherapy Ii Congress London, England July 1975 Xviii+618p Illus Plenum Press: New York, N Y , U S A ; London, England Isbn 0-306-38228-8 437-444

Mickwitz, C.U.; Gaertner, H.; Zantow, K., 1975: Conversion of v.Ardenne-Westmeyer's ultramicrotome into a pyramid-trimming apparatus. Zeitschrift für Medizinische Labortechnik 16(1): 16-20

Uckermann D.; Steinau H U.; Biemer E., 1986: Resurfacing of the sole. Langenbecks Archiv fuer Chirurgie 369: 768

Salas, M.; Eckhardt, L.A., 2003: Critical role for the Oct-2/OCA-B partnership in Ig-secreting cells. B and T lymphocytes arise from a common precursor in the bone marrow, but ultimately acquire very different functions. The difference in function is largely attributable to the expression of tissue-specific transcription factors that activate disc...

Yamato, C.; Takahashi, T.; Kinoshita, K.; Fujita, T., 1982: The metabolic fate of 4-amino-2-(4-butanoyl-hexahydro-1H-1, 4-diazepin-1-yl)-6,7-dimethoxy-quinazoline HCl. 1. 4-Amino-2-(4-butanoyl hexahydro-1H-1, 4-diazepin-1-yl)-6, 7-dimethoxy [2-14C]quinazoline HCl (14C-DDQ) is rapidly absorbed in rats and rabbits and excreted mainly into faeces via the bile. 2. The main metabolites in tissues and excreta are O- a...

Janvier, Sébastien.; Heveker, N., 2005: Mystery upon the origin for the selection of AIDS-protective CCR5Delta32. Medecine Sciences 21(6-7): 577-579

Borawa, JC.; Kerby, JH.; Huish, MT.; Mullis, AW., 1978: Currituck sound fish populations before and after infestation by Eurasian water-milfoil. Proceedings of the Annual Conference Southeastern Association of Fish and Wildlife Agencies, 32: 520-528

Epelde-Elezcano, N.; Duque-Redondo, E.; Martínez-Martínez, V.; Manzano, H.; López-Arbeloa, Iñigo., 2014: Preparation, photophysical characterization, and modeling of LDS722/Laponite 2D-ordered hybrid films. A novel hybrid material with promising optical properties for nonlinear optical applications is presented, as formed by LDS 722 organic dye confined in Laponite clay. Thin films of the hybrid material with different dye loadings have been prepared...