title: Direct binding of retromer to human papillomavirus type 16 minor capsid protein L2 mediates endosome exit during viral infection.
abstract: Trafficking of human papillomaviruses to the Golgi apparatus during virus entry requires retromer, an endosomal coat protein complex that mediates the vesicular transport of cellular transmembrane proteins from the endosome to the Golgi apparatus or the plasma membrane. Here we show that the HPV16 L2 minor capsid protein is a retromer cargo, even though L2 is not a transmembrane protein. We show that direct binding of retromer to a conserved sequence in the carboxy-terminus of L2 is required for exit of L2 from the early endosome and delivery to the trans-Golgi network during virus entry. This binding site is different from known retromer binding motifs and can be replaced by a sorting signal from a cellular retromer cargo. Thus, HPV16 is an unconventional particulate retromer cargo, and retromer binding initiates retrograde transport of viral components from the endosome to the trans-Golgi network during virus entry. We propose that the carboxy-terminal segment of L2 protein protrudes through the endosomal membrane and is accessed by retromer in the cytoplasm.
authors.affiliation: Department of Genetics, Yale School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Andreea
authors.initials: A
authors.lastname: Popa
authors.affiliation: Department of Genetics, Yale School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology, Yale School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Megan S
authors.initials: MS
authors.lastname: Harrison
authors.affiliation: Department of Genetics, Yale School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Kylia
authors.initials: K
authors.lastname: Goodner
authors.affiliation: Department of Genetics, Yale School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Teymur
authors.initials: T
authors.lastname: Kazakov
authors.affiliation: Department of Genetics, Yale School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Edward C
authors.initials: EC
authors.lastname: Goodwin
authors.affiliation: Department of Genetics, Yale School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Alex
authors.initials: A
authors.lastname: Lipovsky
authors.affiliation: Department of Cell Biology, Yale School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Burd
authors.affiliation: Department of Genetics, Yale School of Medicine, New Haven, Connecticut, United States of America; Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut, United States of America; Department of Molecular Biophysics & Biochemistry, Yale School of Medicine, New Haven, Connecticut, United States of America; Yale Cancer Center, New Haven, Connecticut, United States of America.
authors.forename: Daniel
authors.initials: D
authors.lastname: DiMaio
mesh_terms: D000956:Antigens, Viral / Q000378:metabolism; D001665:Binding Sites; D002213:Capsid / Q000378:metabolism; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000821:virology*; D011992:Endosomes / Q000821:virology; D006056:Golgi Apparatus / Q000378:metabolism / Q000821:virology; D057809:HEK293 Cells; D006367:HeLa Cells; D052162:Human papillomavirus 16 / Q000378:metabolism*; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction; D053586:Virus Internalization; D057074:Virus Release / Q000502:physiology*
chemical_list: D000956:Antigens, Viral; D036022:Capsid Proteins; C063316:L2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D034741:RNA, Small Interfering