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Fig. 3. Examples of intra-protein interactions necessary for proper biosynthesis. (A) Weak integrators are TM domains that require association with an adjacent TM domain to integrate into the lipid bilayer. Increasing the length of the loop between the two TM domains (as shown on the right) prevents the necessary interactions (shown as zigzag lines) from occurring, possibly because the first TM domain integrates before the necessary interactions can take place (Ota et al., 2000). (B) A strong orientation effector (shown here as a red region) forces TM orientation and integration of adjacent domains that would not integrate independently (purple region).