TY - JOUR
T1 - Higher-order interhelical spatial interactions in membrane proteins
AU - Adamian, Larisa
AU - Jackups, Ronald
AU - Binkowski, T. Andrew
AU - Liang, Jie
N1 - Funding Information:
We thank Drs William DeGrado and Vikas Nanda for valuable discussions. We thank two anonymous referees for insightful and valuable suggestions. We thank Patrick Freeman for design and technical support of data base of triplet structures. We thank all structural biologists for depositing the coordinates of membrane proteins in the Protein Data Bank. This work is supported by National Science Foundation (DBI-0078270 and CAREER DBI-0133856) and American Chemical Society (Petroleum Research Fund, 35616-G7).
PY - 2003/3/14
Y1 - 2003/3/14
N2 - Higher-order interactions are important for protein folding and assembly. We introduce the concept of interhelical three-body interactions as derived from Delaunay triangulation and alpha shapes of protein structures. In addition to glycophorin A, where triplets are strongly correlated with protein stability, we found that tight interhelical triplet interactions exist extensively in other membrane proteins, where many types of triplets occur far more frequently than in soluble proteins. We developed a probabilistic model for estimating the value of membrane helical interaction triplet (MHIT) propensity. Because the number of known structures of membrane proteins is limited, we developed a bootstrap method for determining the 95% confidence intervals of estimated MHIT values. We identified triplets that have high propensity for interhelical interactions and are unique to membrane proteins, e.g. AGF, AGG, GLL, GFF and others. A significant fraction (32%) of triplet types contains triplets that may be involved in interhelical hydrogen bond interactions, suggesting the prevalent and important roles of H-bond in the assembly of TM helices. There are several well-defined spatial conformations for triplet interactions on helices with similar parallel or antiparallel orientations and with similar right-handed or left-handed crossing angles. Often, they contain small residues and correspond to the regions of the closest contact between helices. Sequence motifs such as GG4 and AG4 can be part of the three-body interactions that have similar conformations, which in turn can be part of a higher-order cooperative four residue spatial motif observed in helical pairs from different proteins. In many cases, spatial motifs such as serine zipper and polar clamp are part of triplet interactions. On the basis of the analysis of the archaeal rhodopsin family of proteins, tightly packed triplet interactions can be achieved with several different choices of amino acid residues.
AB - Higher-order interactions are important for protein folding and assembly. We introduce the concept of interhelical three-body interactions as derived from Delaunay triangulation and alpha shapes of protein structures. In addition to glycophorin A, where triplets are strongly correlated with protein stability, we found that tight interhelical triplet interactions exist extensively in other membrane proteins, where many types of triplets occur far more frequently than in soluble proteins. We developed a probabilistic model for estimating the value of membrane helical interaction triplet (MHIT) propensity. Because the number of known structures of membrane proteins is limited, we developed a bootstrap method for determining the 95% confidence intervals of estimated MHIT values. We identified triplets that have high propensity for interhelical interactions and are unique to membrane proteins, e.g. AGF, AGG, GLL, GFF and others. A significant fraction (32%) of triplet types contains triplets that may be involved in interhelical hydrogen bond interactions, suggesting the prevalent and important roles of H-bond in the assembly of TM helices. There are several well-defined spatial conformations for triplet interactions on helices with similar parallel or antiparallel orientations and with similar right-handed or left-handed crossing angles. Often, they contain small residues and correspond to the regions of the closest contact between helices. Sequence motifs such as GG4 and AG4 can be part of the three-body interactions that have similar conformations, which in turn can be part of a higher-order cooperative four residue spatial motif observed in helical pairs from different proteins. In many cases, spatial motifs such as serine zipper and polar clamp are part of triplet interactions. On the basis of the analysis of the archaeal rhodopsin family of proteins, tightly packed triplet interactions can be achieved with several different choices of amino acid residues.
KW - Alpha shape
KW - Hydrogen bond
KW - Membrane protein
KW - Structure clustering
KW - Three-body interaction
UR - http://www.scopus.com/inward/record.url?scp=0037436390&partnerID=8YFLogxK
U2 - 10.1016/S0022-2836(03)00041-X
DO - 10.1016/S0022-2836(03)00041-X
M3 - Article
C2 - 12614623
AN - SCOPUS:0037436390
SN - 0022-2836
VL - 327
SP - 251
EP - 272
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
IS - 1
ER -