Fluctuation dynamics analysis of gp120 envelope protein reveals a topologically based communication network.
Human Immunodeficiency Virus (HIV) infection is initiated by binding of the viral glycoprotein gp120, to the cellular receptor CD4. On CD4 binding, gp120 undergoes conformational change, permitting binding to the chemokine receptor. Crystal structures of gp120 ternary complex reveal the CD4 bound conformation of gp120. We report here the application of the Gaussian network model (GNM) to the crystal structures of gp120 bound to CD4 or CD4 mimic and 17b, to study the collective motions of the gp120 core and determine the communication propensities of the residue network. The GNM fluctuation profiles identify residues in the inner domain and outer domain that may facilitate conformational change or stability, respectively. Communication propensities delineate a residue network that is topologically suited for signal propagation from the Phe43 cavity throughout the gp120 outer domain. These results provide a new context for interpreting gp120 core envelope structure-function relationships.
Shrivastava
Indira
I
Department of Computational Biology, School of Medicine, University of Pittsburgh, 3083 Biomedical Science Tower 3, 3501 Fifth Avenue, Pittsburgh, PA 15213, USA. ihs2@pitt.edu
LaLonde
Judith M
JM
D015704:CD4 Antigens / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D015398:Signal Transduction
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120