Sequence specificity in the dimerization of transmembrane alpha-helices
- PMID: 1463743
- DOI: 10.1021/bi00166a002
Sequence specificity in the dimerization of transmembrane alpha-helices
Abstract
While several reports have suggested a role for helix-helix interactions in membrane protein oligomerization, there are few direct biochemical data bearing on this subject. Here, using mutational analysis, we show that dimerization of the transmembrane alpha-helix of glycophorin A in a detergent environment is spontaneous and highly specific. Very subtle changes in the side-chain structure at certain sensitive positions disrupt the helix-helix association. These sensitive positions occur at approximately every 3.9 residues along the helix, consistent with their comprising the interface of a closely fit transmembranous supercoil of alpha-helices. By contrast with other reported cases of interactions between transmembrane helices, the set of interfacial residues in this case contains no highly polar groups. Amino acids with aliphatic side chains define much of the interface, indicating that precise packing interactions between the helices may provide much of the energy for association. These data highlight the potential general importance of specific interactions between the hydrophobic anchors of integral membrane proteins.
Similar articles
-
The glycophorin A transmembrane domain dimer: sequence-specific propensity for a right-handed supercoil of helices.Biochemistry. 1992 Dec 29;31(51):12726-32. doi: 10.1021/bi00166a003. Biochemistry. 1992. PMID: 1463744
-
Sequence dependence of BNIP3 transmembrane domain dimerization implicates side-chain hydrogen bonding and a tandem GxxxG motif in specific helix-helix interactions.J Mol Biol. 2006 Dec 15;364(5):974-90. doi: 10.1016/j.jmb.2006.09.065. Epub 2006 Sep 29. J Mol Biol. 2006. PMID: 17049556
-
Insights into the recognition and association of transmembrane alpha-helices. The free energy of alpha-helix dimerization in glycophorin A.J Am Chem Soc. 2005 Jun 15;127(23):8478-84. doi: 10.1021/ja050581y. J Am Chem Soc. 2005. PMID: 15941282
-
Dimerization of glycophorin A transmembrane helices: mutagenesis and modeling.Soc Gen Physiol Ser. 1993;48:11-21. Soc Gen Physiol Ser. 1993. PMID: 8503039 Review. No abstract available.
-
Ca2+ -ATPase structure in the E1 and E2 conformations: mechanism, helix-helix and helix-lipid interactions.Biochim Biophys Acta. 2002 Oct 11;1565(2):246-66. doi: 10.1016/s0005-2736(02)00573-4. Biochim Biophys Acta. 2002. PMID: 12409199 Review.
Cited by
-
Fluorophores, environments, and quantification techniques in the analysis of transmembrane helix interaction using FRET.Biopolymers. 2015 Jul;104(4):247-64. doi: 10.1002/bip.22667. Biopolymers. 2015. PMID: 25968159 Free PMC article. Review.
-
Detergent properties influence the stability of the glycophorin A transmembrane helix dimer in lysophosphatidylcholine micelles.Biophys J. 2012 Dec 19;103(12):2455-64. doi: 10.1016/j.bpj.2012.11.004. Epub 2012 Dec 18. Biophys J. 2012. PMID: 23260047 Free PMC article.
-
Structural Determinant of β-Amyloid Formation: From Transmembrane Protein Dimerization to β-Amyloid Aggregates.Biomedicines. 2022 Oct 29;10(11):2753. doi: 10.3390/biomedicines10112753. Biomedicines. 2022. PMID: 36359274 Free PMC article. Review.
-
Bypassing antibiotic selection: positive screening of genetically modified cells with an antigen-dependent proliferation switch.Nucleic Acids Res. 2003 Apr 1;31(7):e32. doi: 10.1093/nar/gng032. Nucleic Acids Res. 2003. PMID: 12655020 Free PMC article.
-
Polar residues drive association of polyleucine transmembrane helices.Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2250-5. doi: 10.1073/pnas.041593698. Epub 2001 Feb 13. Proc Natl Acad Sci U S A. 2001. PMID: 11226225 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Other Literature Sources