Human herpesvirus 7 U21 tetramerizes to associate with class I major histocompatibility complex molecules. J Virol 2014 Mar;88(6):3298-308
Date
01/07/2014Pubmed ID
24390327Pubmed Central ID
PMC3957921DOI
10.1128/JVI.02639-13Scopus ID
2-s2.0-84894543495 (requires institutional sign-in at Scopus site) 14 CitationsAbstract
UNLABELLED: The U21 gene product from human herpesvirus 7 binds to and redirects class I major histocompatibility complex (MHC) molecules to a lysosomal compartment. The molecular mechanism by which U21 reroutes class I MHC molecules to lysosomes is not known. Here, we have reconstituted the interaction between purified soluble U21 and class I MHC molecules, suggesting that U21 does not require additional cellular proteins to interact with class I MHC molecules. Our results demonstrate that U21, itself predicted to contain an MHC class I-like protein fold, interacts tightly with class I MHC molecules as a tetramer, in a 4:2 stoichiometry. These observations have helped to elucidate a refined model describing the mechanism by which U21 escorts class I MHC molecules to the lysosomal compartment.
IMPORTANCE: In this report, we show that the human herpesvirus 7 (HHV-7) immunoevasin U21, itself a class I MHC-like protein, binds with high affinity to class I MHC molecules as a tetramer and escorts them to lysosomes, where they are degraded. While many class I MHC-like molecules have been described in detail, this unusual viral class I-like protein functions as a tetramer, associating with class I MHC molecules in a 4:2 ratio, illuminating a functional significance of homooligomerization of a class I MHC-like protein.
Author List
May NA, Wang Q, Balbo A, Konrad SL, Buchli R, Hildebrand WH, Schuck P, Hudson AWAuthor
Amy W. Hudson PhD Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Carrier ProteinsHerpesvirus 7, Human
Histocompatibility Antigens Class I
Humans
Protein Binding
Protein Multimerization
Roseolovirus Infections
Viral Proteins
