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Helix Packing and Orientation in the Transmembrane Dimer of gp55-P of the Spleen Focus Forming Virus

Wei Liu ^*, Evan Crocker , Stefan N. Constantinescu  and Steven O. Smith ^*

^* Department of Biochemistry and Cell Biology, Center for Structural Biology and Department of Physics and Astronomy, Stony Brook University, Stony Brook, New York 11794; and Ludwig Institute for Cancer Research, Belgium Christian de Duve Institute of Cellular Pathology, MEXP Unit, Université de Louvain, Brussels 1200, Belgium

Correspondence: Address reprint requests to Steven O. Smith, Dept. of Biochemistry and Cell Biology Z = 5215, Stony Brook University, Stony Brook, NY 11794-5215; Tel.: 631-632-1210; Fax: 631-632-8575; E-mail: steven.o.smith{at}sunysb.edu.

gp55-P is a dimeric membrane protein with a single transmembrane helix that is coded by the env gene of the polycythemic strain of the spleen focus forming virus. gp55-P activates the erythropoietin (Epo) receptor through specific transmembrane helix interactions, leading to Epo-independent growth of erythroid progenitors and eventually promoting erythroleukemia. We describe the use of magic angle spinning deuterium NMR to establish the structure of the transmembrane dimer of gp55-P in model membranes. Comparison of the deuterium lineshapes of leucines in the center (Leu^396–399) and at the ends (Leu³⁸⁵, Leu⁴⁰⁷) of the transmembrane sequence shows that gp55-P has a right-handed crossing angle with Leu³⁹⁹ packed in the dimer interface. We discuss the implications of the structure of the gp55-P transmembrane dimer for activation of the Epo receptor.