The reovirus sigma1 aspartic acid sandwich: a trimerization motif poised for conformational change.
Reovirus attachment protein sigma1 mediates engagement of receptors on the surface of target cells and undergoes dramatic conformational rearrangements during viral disassembly in the endocytic pathway. The sigma1 protein is a filamentous, trimeric molecule with a globular beta-barrel head domain. An unusual cluster of aspartic acid residues sandwiched between hydrophobic tyrosines is located at the sigma1 subunit interface. A 1.75-A structure of the sigma1 head domain now reveals two water molecules at the subunit interface that are held strictly in position and interact with neighboring residues. Structural and biochemical analyses of mutants affecting the aspartic acid sandwich indicate that these residues and the corresponding chelated water molecules act as a plug to block the free flow of solvent and stabilize the trimer. This arrangement of residues at the sigma1 head trimer interface illustrates a new protein design motif that may confer conformational mobility during cell entry.
Schelling
Pierre
P
Interfakultäres Institut für Biochemie, Universität Tübingen, Hoppe-Seyler-Strasse 4, D-72076 Tübingen, Germany.
Guglielmi
Kristen M
KM
Kirchner
Eva
E
Paetzold
Bernhard
B
Dermody
Terence S
TS
Stehle
Thilo
T
D020816:Amino Acid Motifs; D001224:Aspartic Acid / Q000235:genetics / Q000378:metabolism*; D036022:Capsid Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D030102:Orthoreovirus, Mammalian / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D040681:Structural Homology, Protein
D036022:Capsid Proteins; D015815:Cell Adhesion Molecules; D021122:Protein Subunits; C031728:sigma 1 protein, reovirus; D001224:Aspartic Acid