2N1R

NMR Structure of the Myristylated Feline Immunodeficiency Virus Matrix Protein

Summary for 2N1R

• Entry DOI: 10.2210/pdb2n1r/pdb
• NMR Information: BMRB: 25573
• Descriptor: Matrix protein p15 (1 entity in total)
• Functional Keywords: myristoylated, fiv, hiv, siv, feline, matrix, p15, viral protein
• Biological source: Feline immunodeficiency virus (isolate Petaluma) (FIV)
• Cellular location: Matrix protein p15: Virion . Capsid protein p24: Virion . Nucleocapsid protein p13: Virion : P16087
• Total number of polymer chains: 1
• Total formula weight: 14728.98

Authors

Brown, L.A.,Cox, C.,Button, R.J.,Baptiste, J.,Bahlow, K.,Spurrier, V.,Luttge, B.G.,Kuo, L.,Freed, E.O.,Summers, M.F.,Kyser, J.,Summers, H.R. (deposition date: 2015-04-15, release date: 2015-05-27, Last modification date: 2023-06-14)

Primary citation

Brown, L.A.,Cox, C.,Baptiste, J.,Summers, H.,Button, R.,Bahlow, K.,Spurrier, V.,Kyser, J.,Luttge, B.G.,Kuo, L.,Freed, E.O.,Summers, M.F.
NMR structure of the myristylated feline immunodeficiency virus matrix protein.
Viruses, 7:2210-2229, 2015

PubMed Abstract: Membrane targeting by the Gag proteins of the human immunodeficiency viruses (HIV types-1 and -2) is mediated by Gag's N-terminally myristylated matrix (MA) domain and is dependent on cellular phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2]. To determine if other lentiviruses employ a similar membrane targeting mechanism, we initiated studies of the feline immunodeficiency virus (FIV), a widespread feline pathogen with potential utility for development of human therapeutics. Bacterial co-translational myristylation was facilitated by mutation of two amino acids near the amino-terminus of the protein (Q5A/G6S; myrMAQ5A/G6S). These substitutions did not affect virus assembly or release from transfected cells. NMR studies revealed that the myristyl group is buried within a hydrophobic pocket in a manner that is structurally similar to that observed for the myristylated HIV-1 protein. Comparisons with a recent crystal structure of the unmyristylated FIV protein [myr(-)MA] indicate that only small changes in helix orientation are required to accommodate the sequestered myr group. Depletion of PI(4,5)P2 from the plasma membrane of FIV-infected CRFK cells inhibited production of FIV particles, indicating that, like HIV, FIV hijacks the PI(4,5)P2 cellular signaling system to direct intracellular Gag trafficking during virus assembly.

PubMed: 25941825
DOI: 10.3390/v7052210

Experimental method

SOLUTION NMR