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Volumn 328, Issue 5976, 2010, Pages 357-360

Structural basis of preexisting immunity to the 2009 H1N1 pandemic influenza virus

Author keywords

[No Author keywords available]

Indexed keywords

ENVELOPE PROTEIN; INFLUENZA VACCINE; NEUTRALIZING ANTIBODY; VIRUS HEMAGGLUTININ;

EID: 77951165843     PISSN: 00368075     EISSN: 10959203     Source Type: Journal    
DOI: 10.1126/science.1186430     Document Type: Article
Times cited : (518)

References (39)
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    • The RMSD between the membrane-distal domain of CA04 to other H1 HA structures [as Protein Data Bank identification codes (PDB IDs)] are as follows: 1RD8 (A/South Carolina/1/18, 0.58 Å); IRUZ (A/South Carolina/ 1/18, 0.76 Å); 1RU7 (A/Puerto Rico/8/34, 0.63 Å); 1RUY (A/swine/lowa/15/1930, 0.62 Å); 3HTO (A/wild duck/ Jiangxi/12416/2005, 0.60 Å).
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    • In the crystal structures of H1 HA, the three peptide segments composing the Sa site are all anchored at both ends by aromatic residues whose side chains are buried inside the HA1 receptor binding domain. These residues are absolutely conserved in all H1 HAs, and the numbers of residues between these hydrophobic anchors remain the same, thus maintaining the structural integrity of the Sa site. Across different subtypes, however, these aromatic residues are less well conserved, and slight variations in the length of the component peptide segments may occur.
    • In the crystal structures of H1 HA, the three peptide segments composing the Sa site are all anchored at both ends by aromatic residues whose side chains are buried inside the HA1 receptor binding domain. These residues are absolutely conserved in all H1 HAs, and the numbers of residues between these hydrophobic anchors remain the same, thus maintaining the structural integrity of the Sa site. Across different subtypes, however, these aromatic residues are less well conserved, and slight variations in the length of the component peptide segments may occur.
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    • Indeed, the electron density is weak in this region and is probably only present at all because of a weak crystal contact to an adjacent HA molecule.
    • Indeed, the electron density is weak in this region and is probably only present at all because of a weak crystal contact to an adjacent HA molecule.
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    • Single-letter abbreviations for the amino acid residues are as follows: A, Ala; C, Cys; D, Asp; E, Glu; F, Phe; G, Gly; H, His; I, He; K, Lys; L, Leu; M, Met; N, Asn; P, Pro; Q, GIn; R, Arg; S, Ser; T, Thr; V, Val; W, Trp; and Y, Tyr.
    • Single-letter abbreviations for the amino acid residues are as follows: A, Ala; C, Cys; D, Asp; E, Glu; F, Phe; G, Gly; H, His; I, He; K, Lys; L, Leu; M, Met; N, Asn; P, Pro; Q, GIn; R, Arg; S, Ser; T, Thr; V, Val; W, Trp; and Y, Tyr.
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    • note
    • The work was supported in part by NIH grants AI058113 (I.A.W., J.E.C, and P. Palese) and AI057157 (J.E.C.), predoctoral fellowships from the Achievement Rewards for College Scientists Foundation and the NIH Molecular Evolution Training Program GM080209 (D.C.E.), and the Skaggs Institute for Chemical Biology. X-ray diffraction data sets were collected at the Stanford Synchrotron Radiation Lightsource beamline 9-2 and at the Advanced Photon Source beamline 23ID-B (GM/CA-CAT). The GM/CA CAT 23-ID-B beamline has been funded in whole or in part with federal funds from National Cancer Institute (Y1-CO-1020) and National Institute of General Medical Sciences (Y1-GM-1104). Use of the Advanced Photon Source (APS) was supported by the U.S. Department of Energy, Basic Energy Sciences, Office of Science, under contract no. DE-AC02-06CH11357. We thank P. Palese (Mount Sinai School of Medicine) for providing the CA04 clone and helpful comments, X. Dai and M. A. Elsliger (Scripps Research Institute) and C J. Huffman (Vanderbilt University) for expert technical assistance, H. Tien and D. Marciano of the Robotics Core at the Joint Center for Structural Genomics for automated crystal screening, and M. Becker and the staff of the APS GM/CA CAT 23-ID-B for beamline support. This is publication 20395 from the Scripps Research Institute. Coordinates and structure factors are deposited in the PDB [3LZG for CA04 HA (two trimers) and 3LZF for 1918 HA/2D1 complex]. Vanderbilt University has applied for a provisional patent covering the diagnostic and therapeutic use of antibodies described in this paper. J.E.C. Jr. is a founder of the vaccine company Corbeau Biotech LLC and has consulted for Medlmmune, Novartis, Sanofi, and lmmunobiosciences. J.C.K. is funded by a Pediatric Infectious Diseases Society Fellowship funded by Medlmmune and AstraZeneca.


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