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result sql = The structure of a cytolytic alpha-helical toxin pore reveals its assembly mechanism.
The structure of a cytolytic alpha-helical toxin pore reveals its assembly mechanism.
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char = l;code = 108
char = y;code = 121
char = E;code = 69
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = -;code = 45
char = P;code = 80
char = F;code = 70
char = T;code = 84
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = l;code = 108
char = y;code = 121
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = -;code = 45
char = h;code = 104
char = e;code = 101
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = i;code = 105
char = b;code = 98
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = e;code = 101
char = m;code = 109
char = o;code = 111
char = l;code = 108
char = y;code = 121
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = p;code = 112
char = h;code = 104
char = e;code = 101
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = y;code = 121
char = p;code = 112
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = E;code = 69
char = s;code = 115
char = c;code = 99
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = c;code = 99
char = h;code = 104
char = i;code = 105
char = a;code = 97
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = S;code = 83
char = a;code = 97
char = l;code = 108
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = a;code = 97
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = C;code = 67
char = l;code = 108
char = y;code = 121
char = A;code = 65
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = t;code = 116
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = w;code = 119
char = a;code = 97
char = r;code = 114
char = d;code = 100
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = m;code = 109
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = p;code = 112
char = o;code = 111
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = i;code = 105
char = s;code = 115
char = s;code = 115
char = u;code = 117
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = v;code = 118
char = a;code = 97
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = E;code = 69
char = l;code = 108
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = s;code = 115
char = c;code = 99
char = o;code = 111
char = p;code = 112
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = o;code = 111
char = l;code = 108
char = u;code = 117
char = b;code = 98
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = C;code = 67
char = l;code = 108
char = y;code = 121
char = A;code = 65
char = ;code = 32
char = m;code = 109
char = u;code = 117
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = u;code = 117
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = r;code = 114
char = g;code = 103
char = o;code = 111
char = ;code = 32
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = g;code = 103
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = g;code = 103
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = m;code = 109
char = e;code = 101
char = m;code = 109
char = b;code = 98
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = .;code = 46
char = ;code = 32
char = H;code = 72
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = p;code = 112
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = 3;code = 51
char = .;code = 46
char = 3;code = 51
char = ;code = 32
char = A;code = 65
char = ;code = 32
char = c;code = 99
char = r;code = 114
char = y;code = 121
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = 4;code = 52
char = 0;code = 48
char = 0;code = 48
char = ;code = 32
char = k;code = 107
char = D;code = 68
char = a;code = 97
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = d;code = 100
char = e;code = 101
char = c;code = 99
char = a;code = 97
char = m;code = 109
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = m;code = 109
char = e;code = 101
char = m;code = 109
char = b;code = 98
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = C;code = 67
char = l;code = 108
char = y;code = 121
char = A;code = 65
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = t;code = 116
char = i;code = 105
char = a;code = 97
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = C;code = 67
char = l;code = 108
char = y;code = 121
char = A;code = 65
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = o;code = 111
char = l;code = 108
char = u;code = 117
char = b;code = 98
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = r;code = 114
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = v;code = 118
char = o;code = 111
char = l;code = 108
char = v;code = 118
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = l;code = 108
char = f;code = 102
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = d;code = 100
char = u;code = 117
char = e;code = 101
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = t;code = 116
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = g;code = 103
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = g;code = 103
char = e;code = 101
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = u;code = 117
char = p;code = 112
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = 1;code = 49
char = 4;code = 52
char = 0;code = 48
char = ;code = 32
char = A;code = 65
char = ,;code = 44
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = o;code = 111
char = r;code = 114
char = g;code = 103
char = a;code = 97
char = n;code = 110
char = i;code = 105
char = z;code = 122
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = h;code = 104
char = y;code = 121
char = d;code = 100
char = r;code = 114
char = o;code = 111
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = b;code = 98
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = -;code = 45
char = s;code = 115
char = h;code = 104
char = e;code = 101
char = e;code = 101
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = o;code = 111
char = p;code = 112
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = -;code = 45
char = h;code = 104
char = e;code = 101
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = e;code = 101
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = g;code = 103
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = g;code = 103
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = q;code = 113
char = u;code = 117
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = i;code = 105
char = s;code = 115
char = m;code = 109
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = m;code = 109
char = b;code = 98
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = e;code = 101
char = r;code = 114
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
result sql = Pore-forming toxins (PFTs) are a class of potent virulence factors that convert from a soluble form to a membrane-integrated pore. They exhibit their toxic effect either by destruction of the membrane permeability barrier or by delivery of toxic components through the pores. Among the group of bacterial PFTs are some of the most dangerous toxins, such as diphtheria and anthrax toxin. Examples of eukaryotic PFTs are perforin and the membrane-attack complex, proteins of the immune system. PFTs can be subdivided into two classes, alpha-PFTs and beta-PFTs, depending on the suspected mode of membrane integration, either by alpha-helical or beta-sheet elements. The only high-resolution structure of a transmembrane PFT pore is available for a beta-PFT--alpha-haemolysin from Staphylococcus aureus. Cytolysin A (ClyA, also known as HlyE), an alpha-PFT, is a cytolytic -helical toxin responsible for the haemolytic phenotype of several Escherichia coli and Salmonella enterica strains. ClyA is cytotoxic towards cultured mammalian cells, induces apoptosis of macrophages and promotes tissue pervasion. Electron microscopic reconstructions demonstrated that the soluble monomer of ClyA must undergo large conformational changes to form the transmembrane pore. Here we report the 3.3 A crystal structure of the 400 kDa dodecameric transmembrane pore formed by ClyA. The tertiary structure of ClyA protomers in the pore is substantially different from that in the soluble monomer. The conversion involves more than half of all residues. It results in large rearrangements, up to 140 A, of parts of the monomer, reorganization of the hydrophobic core, and transitions of -sheets and loop regions to -helices. The large extent of interdependent conformational changes indicates a sequential mechanism for membrane insertion and pore formation.

Publication: Nature 2009 Jun 4 ;459(7247)::726-30. :doi: 10.1038/nature08026.
Publication Date: 2009 Jun 4
Study Author(s): Mueller, Marcus;Grauschopf, Ulla;Maier, Timm;Glockshuber, Rudi;Ban, Nenad;
Institution: Institute of Molecular Biology and Biophysics, ETH Zurich, 8093 Zurich, Switzerland.
Shortcut link to this study:
Pore-forming toxins (PFTs) are a class of potent virulence factors that convert from a soluble form to a membrane-integrated pore. They exhibit their toxic effect either by destruction of the membrane permeability barrier or by delivery of toxic components through the pores. Among the group of bacterial PFTs are some of the most dangerous toxins, such as diphtheria and anthrax toxin. Examples of eukaryotic PFTs are perforin and the membrane-attack complex, proteins of the immune system. PFTs can be subdivided into two classes, alpha-PFTs and beta-PFTs, depending on the suspected mode of membrane integration, either by alpha-helical or beta-sheet elements. The only high-resolution structure of a transmembrane PFT pore is available for a beta-PFT--alpha-haemolysin from Staphylococcus aureus. Cytolysin A (ClyA, also known as HlyE), an alpha-PFT, is a cytolytic -helical toxin responsible for the haemolytic phenotype of several Escherichia coli and Salmonella enterica strains. ClyA is cytotoxic towards cultured mammalian cells, induces apoptosis of macrophages and promotes tissue pervasion. Electron microscopic reconstructions demonstrated that the soluble monomer of ClyA must undergo large conformational changes to form the transmembrane pore. Here we report the 3.3 A crystal structure of the 400 kDa dodecameric transmembrane pore formed by ClyA. The tertiary structure of ClyA protomers in the pore is substantially different from that in the soluble monomer. The conversion involves more than half of all residues. It results in large rearrangements, up to 140 A, of parts of the monomer, reorganization of the hydrophobic core, and transitions of -sheets and loop regions to -helices. The large extent of interdependent conformational changes indicates a sequential mechanism for membrane insertion and pore formation.
PMID: 19421192

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