title: Zinc- and pH-dependent conformational transition in a putative interdomain linker region of the influenza virus matrix protein M1.
abstract: The matrix protein M1 of influenza A virus forms a shell beneath the viral envelope and sustains the virion architecture by interacting with other viral components. A structural change of M1 upon acidification of the virion interior in an early stage of virus infection is considered to be a key step to virus uncoating. We examined the structure of a 28-mer peptide (M1Lnk) representing a putative linker region between the N- and C-terminal domains of M1 by using circular dichroism, Raman, and absorption spectroscopy. M1Lnk assumes an alpha-helical structure in a mildly hydrophobic environment irrespective of pH, being consistent with the X-ray crystal structures of an N-terminal fragment of M1 at pH 7 and 4. In the presence of Zn(2+), on the other hand, M1Lnk takes a partially unfolded conformation at neutral pH with a tetrahedral coordination of two Cys residues and two His residues to a Zn(2+) ion in the central part of the peptide. Upon acidification, the peptide releases the Zn(2+) ion and refolds into the alpha-helix-rich structure with a midpoint of transition at pH 5.9. The pH-dependent conformational transition of M1Lnk strongly suggests that the interdomain linker region of M1 also undergoes a pH-dependent unfolding-refolding transition in the presence of Zn(2+). A small but significant portion of the M1 protein is bound to Zn(2+) in the virion, and the Zn(2+)-bound M1 molecule may play a special role in virus uncoating by changing the disposition of the N- and C-terminal domains upon acidification of the virion interior.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Sendai 980-8578, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Okada
authors.forename: Takashi
authors.initials: T
authors.lastname: Miura
authors.forename: Hideo
authors.initials: H
authors.lastname: Takeuchi
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D002413:Cations, Divalent / Q000737:chemistry; D002942:Circular Dichroism; D003035:Cobalt / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009980:Influenza A virus / Q000737:chemistry*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013059:Spectrum Analysis, Raman; D014763:Viral Matrix Proteins / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry*
chemical_list: D002413:Cations, Divalent; C031540:M-protein, influenza virus; C488936:M1 protein, Influenza A virus; D010446:Peptide Fragments; D014763:Viral Matrix Proteins; D003035:Cobalt; D015032:Zinc