Fig 1.
The domain swapping mechanism, demonstrated on the formation of a dimeric oligomer.
(a) Two monomers with their folded potential hinge regions. (b) The monomers with their open hinge regions. (c) The dimerization, leading to the domain-swapped oligomer.
Fig 2.
The running ruler method demonstrated on the engineered N-terminal domain of CD2 protein (PDB code: 1A64), starting from the N-terminal; running ruler size (red): seven amino-acids (h = 7).
(a) The first segment, 1st-7th amino acids segments-pairs. (b) The second segment, 2nd-8th amino acids segments-pairs. (c) The third segment, 3rd -9th amino acids segments-pairs.
Fig 3.
Running ruler symmetry analysis applied on RNase A N-terminal swapped dimer (PDB code: 1A2W).
(a) Cartoon representation of the protein. Each subunit is indicated by a different color (blue and green), and the originally proposed hinge region is colored red. (b) CSM spectrum of the protein, the ruler size is as the length of the hinge region (8 amino acids). The black arrow indicates the hinge region. (c) CSM spectrum of the protein with a ruler size of 10 amino acids. The black arrow indicates the hinge region. For data source see ref. [38].
Fig 4.
The proteins structures analyzed in Fig 5.
Each subunit is indicated by a different color, and the originally proposed hinge region is colored red. (a) N-terminal domain of CD2 (PDB code: 1CDC), (b) Diabody (PDB code: 1LMK), (c) Engineered N-terminal domain of CD2 (PDB code: 1A64), (d) Interleukin-5 (IL-5, PDB code: 1HUL), (e) TrkA-d4 dimer (PDB code: 1WWA). For data sources see ref.'s [39–43].
Fig 5.
Running ruler symmetry analysis applied on proteins involved in 3D domain swapping.
The black arrow indicates the hinge region; other colored arrows are explained in the text. (a) N-terminal domain of CD2, hinge region: 44–50, (b) Diabody, hinge region: 123–127, (c) Engineered N-terminal domain of CD2, hinge region: 44–50, (d) Interleukin-5 (IL-5), hinge region: 82–89, (e) TrkA-d4 dimer, hinge region: black– 297–299, red– 295–299. See Fig 4 for their PDB codes and cartoon representation and Table 1 for more information.
Fig 6.
Additional running ruler symmetry analyses (see also S2 Fig); the neighborhood of the hinge region is shown.
Black arrows—the hinge region. (a) Bovine seminal ribonuclease (PDB code: 1BSR), (b) β-crystallin (PDB code: 1BLB), (c) Human pancreatic ribonuclease chimera (PDB code: 1H8X), (d) RNase A N-terminal timer (PDB code: 1JS0), (e) Human glyoxalase I dimer (PDB code: 1BH5), (f) α-spectrin (PDB code: 2SPC), (g) Amyloid-like Cystatin C (PDB code: 1TIJ), (h) SH3 domain of Eps8 (PDB code: 1AOJ), (i) Circadian Clock Protein KaiA (PDB code: 1R8J), (j) Cyanovirin-N (PDB code: 1L5B), (k) Triggering receptor expressed on myeloid cells 1 (TREM-1) (PDB code: 1Q8M), (l) Cystatin A (PDB code: 1N9J), (m) Grb2-SH2 domain dimer (PDB code: 1FYR), (n) Odorant binding protein dimer (PDB code: 1OBP), (o) Cell division protein FtsZ (PDB code: 1W5F), (p) NrdH-redoxin (PDB code: 1R7H). See Table 1 for more information. For data sources see ref.'s [44–59].
Table 1.
Hinge region location.
Fig 7.
Focus on the origin of the symmetry distortion: each subunit is indicated by different color.
(a) N-terminal domain of CD2 (PDB code: 1A64) from two different points of view. The amino-acids segments 21–28 and 81–88 are indicated by sticks representation. The interaction between those segments causes the symmetry distortion. These over-crowded regions are surrounded by red circles. (b) Interleukin-5 (PDB code: 1HUL). The regions which are indicated by colored arrows in Fig 5D are colored here respectively. The marked interaction area is seen from two different points of view. For data sources see ref.'s [41,42].
Table 2.
Probability analysis of symmetry distortion at the hinge range.