The construction of portions of a protein provides information about its functional mechanisms. Peptide engineering is a recently developed technique to construct a small tertiary structure or a portion of a protein, and allows expansion to applications for bio- and physicochemistries. In this article, we focus on the class A scavenger receptor, which plays a key role in atherogenesis, and may be involved in other pathogenic processes. The receptor is mainly composed of simple tertiary structures, such as collagen and α-helical coiled coil structures, which have different functions. We constructed both the collagen-like and α-helical coiled coil domains by peptide engineering, and analysed the structure-function relationships of the receptor. Understanding the mechanisms of their functions at the amino acid level should help us to mimic the functional domains and to create de novo designed proteins with new functions.
References
1.
CarrC. & KimP. S. (1993) A spring-loaded mechanism for the conformational change of influenza hemagglutinin. Cell, 73, 823–832.
2.
CochranA. G. & KimP. S. (1996) Imitation of Escherichia coli aspartate receptor signaling in engineered dimers of the cytoplasmic domain. Science, 271, 1113–1116.
3.
MontalM., MontalM. S. & TomichJ. M. (1990) Synporins-synthetic proteins that emulate the pore structure of biological ionic channels. Proc. Natl. Acad. Sci. USA, 87, 6929–6933.
4.
TripetB., ValeR. D. & HodgeR. S. (1997) Demonstration of coiled-coil interactions within the kinesin neck region using synthetic peptides. Implications for motor activity. J. Biol. Chem., 272, 8946–8956.
5.
BrysonJ. W., BetzS. F., LuH. S., SuichD. J., ZhouH. X., O'NeilK. T. & DeGradoW. F. (1995) Protein design: A hierarchic approach. Science, 270, 935–941.
6.
KohnW. D. & HodgesR. S. (1998) De novo design of α-helical coiled coils and bundles: models for the development of protein-design principles. Trends Biotechnol., 16, 379–389.
7.
FieldsG. B. & ProckopD. J. (1996) Perspectives on the synthesis and application of triple-helical, collagen-model peptides. Biopolymers, 40, 345–357.
8.
BeckK. & BrodskyB. (1998) Supercoiled protein motifs: The collagen triple-helix and the α-helical coiled coil. J. Struct. Biol., 122, 17–29.
9.
SchneiderJ. P. & KellyJ. W. (1995) Templates that induce α-helical, β-sheet, and loop conformations. Chem. Rev., 95, 2169–2187.
10.
TarnJ. P. & SpetzlerJ. C. (1995) Chemoselective approaches to the preparation of peptide dendrimers and branched artificial proteins using unprotected peptides as building blocks. Biomed. Pept. Proteins Nucleic Acids, 1, 123–132.
11.
TanakaT., WadaY., NakamuraH., DoiT., ImanishiT. & KodamaT. (1993) A synthetic model of collagen structure taken from bovine macrophage scavenger receptor. FEBS Lett., 334, 272–276.
12.
PlattN. & GordonS. (1998) Scavenger receptors: diverse activities and promiscuous binding of polyanionic ligands. Chem. Biol., 5, R193–R203.
13.
KriegerM. (1992) Molecular flypaper and atherosclerosis: structure of the macrophage scavenger receptor. Trends Biochem. Sci., 17, 141–146.
14.
El KhouryJ., HickmanS. E., ThomasC. A., CaoL., SilversteinS. C. & LoikeJ. D. (1996) Scavenger receptor-mediated adhesion of microglia to beta-amyloid fibrils. Nature, 382, 716–719.
15.
ArakiN., HigashiT., MoriT., ShibayamaR., KawabeY., KodamaT., TakahashiK., ShichiriM. & HoriuchiS. (1995) Macrophage scavenger receptor mediates the endocytic uptake and degradation of advanced glycation end products of the Maillard reaction. Eur. J. Biochem., 230, 408–415.
16.
FraserI., HughesD. & GordonS. (1993) Divalent cation-independent macrophage adhesion inhibited by monoclonal antibody to murine scavenger receptor. Nature, 364, 343–346.
17.
BrownM. S. & GoldsteinJ. L. (1983) Lipoprotein metabolism in the macrophage: implications for cholesterol deposition in atherosclerosis. Annu. Rev. Biochem., 52, 223–261.
18.
DoiT., KurasawaM., HigashinoK., ImanishiT., MoriT., NaitoM., TakahashiK., KawabeY., WadaY., MatsumotoA. & KodamaT. (1994) The histidine interruption of an alpha-helical coiled coil allosterically mediates a pH-dependent ligand dissociation from macrophage scavenger receptors. J. Biol. Chem., 269, 25598–25604.
19.
TanakaT., NishikawaA., TanakaY., NakamuraH., KodamaT., ImanishiT. & DoiT. (1996) Synthetic collagen-like domain derived from the macrophage scavenger receptor binds acetylated low-density lipoprotein in vitro. Protein Eng., 9, 307–313.
20.
BrodskyB., LiM. H., LongC. G., ApigoJ. & BaumJ. (1992) NMR and CD studies of triple-helical peptides. Biopolymers, 32, 447–451.
21.
TanakaY., SuzukiK. & TanakaT. (1998) Synthesis and stabilization of amino and carboxy terminal constrained collagenous peptidesJ. Peptide Res., 51, 413–119.
22.
FengY., MelaciniG., TaulaneJ. P. & GoodmanM. (1996) Acetyl-terminated and template-assembled collagen-based polypeptide composed Gly-Pro-Hyp sequences. 2. Synthesis and conformational analysis by circular dichroism, ultraviolet absorbance, and optical rotation. J. Am. Chem., Soc.118, 10351-10358.
23.
DoiT., HigashinoK., KuriharaK., WadaY., MiyazakiT., NakamuraH., UesugiS., ImanishiT., KawabeY., ItakuraH., YazakiY., MatsumotoA. & KodamaT. (1993) Charged collagen structure mediates the recognition of negatively charged macromolecules by macrophage scavenger receptors. J. Biol. Chem., 268, 2126–2133.
24.
YamamotoK., NishimuraN., DoiT., ImanishiT., KodamaT., SuzukiK. & TanakaT. (1997) The Lys cluster in the collagen-like domain of the scavenger receptor provides for its ligand binding and ligand specificity. FEBS Lett., 414, 182–186.
25.
PearsonA. M., RichA. & KriegerM. (1993) Polynucleotide binding to macrophage scavenger receptors depends on the formation of base-quartet-stabilized four-stranded helices. J. Biol. Chem., 268, 3546–3554.
26.
MielewczykS. S., BreslauerK. J., AnachiR. B. & BrodskyB. (1996) Binding studies of a triple-helical peptide model of macrophage scavenger receptor to tetraplex nucleic acids. Biochemistry, 35, 11396–11402.
27.
SuzukiK., DoiT., ImanishiT., KodamaT. & TanakaT. (1999) Oligonucleotide aggregates bind to the macrophage scavenger receptor. Eur. J. Biochem., 260, 855–860.
28.
LupasA. (1996) Coiled coils: new structures and new functions. Trends Biochem. Sci., 21, 375–382.
29.
SuzukiK., DoiT., ImanishiT., KodamaT. & TanakaT. (1997) The conformation of the α-helical coiled coil domain of macrophage scavenger receptor is pH dependent. Biochemistry, 36, 15140–15146.
30.
ResnickD., ChattertonJ. E., SchwartzK., SlayterH. & KriegerM. (1996) Structures of class A macrophage scavenger receptors. Electron microscopic study of flexible, multidomain, fibrous proteins and determination of the disulfide bond pattern of the scavenger receptor cysteine-rich domain. J. Biol. Chem., 271, 26924–26930.
31.
SuzukiK., YamadaT. & TanakaT. (1999) Role of the buried glutamate in the α-helical coiled coil domain to the macrophage scavenger receptor. Biochemistry, 38, 1751–1756.
32.
SuzukiK., HiroakiH., KohdaD. & TanakaT. (1998) An isoleucine zipper peptide forms a native-like triple stranded coiled coil in solution. Protein Eng., 11, 1051–1055.
