Figure 4. Structural homology between αB... | Rockefeller University Press

Figure 4.

Structural homology between αB and αC helices of EH2and TM1, ILC1 and H8 of rhodopsin.(A) αB and αC helices from the EH2 domain are highlighted in orange. (B) Closeup of αB and αC helices from A showing NPF interacting side chains. (C) Ground state structure of rhodopsin (PDB accession no. 1U19) with TM1, ICL1, and H8 in reddish-purple. (D) Closeup of TM1, ICL1, and H8 from C. Rhodopsin was oriented to emphasize homology in secondary structure between H8 and the αC helix, and TM1 and the αB helix in B. (E) The sequence of the αB helix from the EH2 domain in B was aligned manually with the sequence of TM1 and ICL1 from rhodopsin in D and multiple sequence alignments from class A GPCRs. Grey boxes indicate residues in the EH2 domain that contact the NPF motif as shown in Fig. 3 B; aligning residues in GPCRs are also in grey boxes. Polar residues Gly, Ser, Thr, Tyr, and Cys are green; neutral residues Gln and Asn are purple; basic residues Lys, Arg, and His are blue; acidic residues Asp and Glu are red; and hydrophobic residues Ala, Val, Leu, Ile, Pro, Trp, Phe, and Met are black. (F) The sequence of the αC helix from the EH2 domain in B was aligned manually with the sequence of H8 from rhodopsin in D and multiple sequence alignments from class A GPCRs. Grey boxes indicate residues in the EH2 domain that contact the NPF motif as shown in Fig. 3 B; aligning residues in GPCRs are also in grey boxes. Residues in the multiple sequence alignment are colored as in E. Asterisks under multiple sequence alignments indicate residues in the αC helix of the EH2 domain that are most critical for interactions with the NPF motif, and by analogy, the residues in H8 that may be most important for interactions with the NPF motif in Gγ.

Structural homology between αB and αC helices of EH ₂ and TM1, ILC1 and H8 of rhodopsin. (A) αB and αC helices from the EH₂ domain are highlighted in orange. (B) Closeup of αB and αC helices from A showing NPF interacting side chains. (C) Ground state structure of rhodopsin (PDB accession no. 1U19) with TM1, ICL1, and H8 in reddish-purple. (D) Closeup of TM1, ICL1, and H8 from C. Rhodopsin was oriented to emphasize homology in secondary structure between H8 and the αC helix, and TM1 and the αB helix in B. (E) The sequence of the αB helix from the EH₂ domain in B was aligned manually with the sequence of TM1 and ICL1 from rhodopsin in D and multiple sequence alignments from class A GPCRs. Grey boxes indicate residues in the EH₂ domain that contact the NPF motif as shown in Fig. 3 B; aligning residues in GPCRs are also in grey boxes. Polar residues Gly, Ser, Thr, Tyr, and Cys are green; neutral residues Gln and Asn are purple; basic residues Lys, Arg, and His are blue; acidic residues Asp and Glu are red; and hydrophobic residues Ala, Val, Leu, Ile, Pro, Trp, Phe, and Met are black. (F) The sequence of the αC helix from the EH₂ domain in B was aligned manually with the sequence of H8 from rhodopsin in D and multiple sequence alignments from class A GPCRs. Grey boxes indicate residues in the EH₂ domain that contact the NPF motif as shown in Fig. 3 B; aligning residues in GPCRs are also in grey boxes. Residues in the multiple sequence alignment are colored as in E. Asterisks under multiple sequence alignments indicate residues in the αC helix of the EH₂ domain that are most critical for interactions with the NPF motif, and by analogy, the residues in H8 that may be most important for interactions with the NPF motif in Gγ.