Mammalian SCAN domain dimer is a domain-swapped homolog of the HIV capsid C-terminal domain.
Retroviral assembly is driven by multiple interactions mediated by the Gag polyprotein, the main structural component of the forming viral shell. Critical determinants of Gag oligomerization are contained within the C-terminal domain (CTD) of the capsid protein, which also harbors a conserved sequence motif, the major homology region (MHR), in the otherwise highly variable Gag. An unexpected clue about the MHR function in retroviral assembly emerges from the structure of the zinc finger-associated SCAN domain we describe here. The SCAN dimer adopts a fold almost identical to that of the retroviral capsid CTD but uses an entirely different dimerization interface caused by swapping the MHR-like element between the monomers. Mutations in retroviral capsid proteins and functional data suggest that a SCAN-like MHR-swapped CTD dimer forms during immature particle assembly. In the SCAN-like dimer, the MHR contributes the major part of the large intertwined dimer interface explaining its functional significance.
Ivanov
Dmitri
D
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Stone
James R
JR
Maki
Jenny L
JL
Collins
Tucker
T
Wagner
Gerhard
G
D000595:Amino Acid Sequence; D036022:Capsid Proteins / Q000737:chemistry* / Q000235:genetics; D019281:Dimerization; D015497:HIV-1 / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D051741:Kruppel-Like Transcription Factors; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D019906:Nuclear Magnetic Resonance, Biomolecular; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D019065:Virus Assembly; D016335:Zinc Fingers / Q000235:genetics
D036022:Capsid Proteins; D051741:Kruppel-Like Transcription Factors; D011994:Recombinant Proteins; D012097:Repressor Proteins; C095634:ZNF174 protein, human