title: Crystal structures of influenza A virus matrix protein M1: variations on a theme.
abstract: Matrix protein 1 (M1) of the influenza A virus plays multiple roles in virion assembly and infection. Interest in the pH dependence of M1's multiple functions led us to study the effect of subtle pH changes on M1 structure, resulting in the elucidation of a unique low-pH crystal structure of the N(1-165)-domain of A/WSN/33 (H1N1) M1 that has never been reported. Although the 2.2 Å crystal structure of M1 N-terminus shows a dimer with the two monomers interacting in a face-to-face fashion at low pH as observed earlier, a 44° rotation of the second monomer has led to a significantly different dimer interface that possibly affects dimer stability. More importantly, while one of the monomers is fully defined, the N-terminal half of the second monomer shows considerable disorder that appears inherent in the protein and is potentially physiologically relevant. Such disorder has not been observed in any other previously reported structure at either low or high pH conditions, despite similar crystallization pH conditions. By comparing our novel N(1-165)-domain structure with other low-pH or neutral-pH M1 structures, it appears that M1 can energetically access different monomer and dimer conformations, as well as oligomeric states, with varying degree of similarities. The study reported here provides further insights into M1 oligomerization that may be essential for viral propagation and infectivity.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy and Institute for Structural Biology and Drug Discovery, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Martin K
authors.initials: MK
authors.lastname: Safo
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy and Institute for Structural Biology and Drug Discovery, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Faik N
authors.initials: FN
authors.lastname: Musayev
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy and Institute for Structural Biology and Drug Discovery, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Philip D
authors.initials: PD
authors.lastname: Mosier
authors.affiliation: Institute of Materia Medica, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China.
authors.forename: Qibing
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Bethesda, Maryland, United States of America.
authors.forename: Hang
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy and Institute for Structural Biology and Drug Discovery, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Umesh R
authors.initials: UR
authors.lastname: Desai
mesh_terms: D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology; D008958:Models, Molecular; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D014763:Viral Matrix Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D014763:Viral Matrix Proteins