Polar residues drive association of polyleucine transmembrane helices.
Although many polar residues are directly involved in transmembrane protein functions, the extent to which they contribute to more general structural features is still unclear. Previous studies have demonstrated that asparagine residues can drive transmembrane helix association through interhelical hydrogen bonding [Choma, C., Gratkowski, H., Lear, J. D. & DeGrado, W. F. (2000) Nat. Struct. Biol. 7, 161-166; and Zhou, F. X., Cocco, M. J., Russ, W. P., Brunger, A. T. & Engelman, D. M. (2000) Nat. Struct. Biol. 7, 154-160]. We have studied the ability of other polar residues to promote helix association in detergent micelles and in biological membranes. Our results show that polyleucine sequences with Asn, Asp, Gln, Glu, and His, residues capable of being simultaneously hydrogen bond donors and acceptors, form homo- or heterooligomers. In contrast, polyleucine sequences with Ser, Thr, and Tyr do not associate more than the polyleucine sequence alone. The results therefore provide experimental evidence that interactions between polar residues in the helices of transmembrane proteins may serve to provide structural stability and oligomerization specificity. Furthermore, such interactions can allow structural flexibility required for the function of some membrane proteins.
Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Ave., New Haven, CT 06520-8114, USA.
F X
FX
Zhou
H J
HJ
Merianos
A T
AT
Brunger
D M
DM
Engelman
D000595:Amino Acid Sequence; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D006860:Hydrogen Bonding; D008565:Membrane Proteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid
D008565:Membrane Proteins; D010455:Peptides; D011993:Recombinant Fusion Proteins; C027819:polyleucine; D015500:Chloramphenicol O-Acetyltransferase