Table I.
Proteins of Which Peptide Fragments have been Shown to Form Amyloid Fibrils In Vitro and for Which a 3D Structural Model Is Available
| Protein | UniProt ID | PDB ID of 3D structural model for proteina | Amyloidogenic sequence(s)/peptide(s) | Location in native mature protein sequence | References |
|---|---|---|---|---|---|
| α-Synuclein | P37840 | 1XQ8a | (68)GAVVTGVTAVA(78) | 68–78 | 68 |
| (51)GVATVA(56) | 51–56 | 57 | |||
| (66)VGGAVVTGV(74) | 66–74 | ||||
| (86)GSIAAAT(92) | 86–92 | ||||
| (71)VTGVTAVAQKTV(82) | 71–82 | 69,70 | |||
| (77)VAQKTV(82) | |||||
| NAC peptide: α-syn(61–95) | 61–95 | 71 | |||
| β-Lactoglobulin | P02754 | 1BEB | (11)DIQKVAGTWY(20) | 11–20 | 72 |
| (101)KYLLFCMENS(110) | 101–110 | ||||
| (116)SLVCQCLVRTP(126) | 116–126 | ||||
| (146)HIRLSFN(152) | 146–152 | ||||
| β2-Microglobulin | P61769 | 1B0G | (20)SNFLNCYVSGFHPSDIEVDLLK(41) | 20–41 | 73 |
| (58)KDWSFY(63) | 58–71 | 74,75,57 | |||
| (59)DWSFYLLYYTEFT(71) | |||||
| (62)FYLLYY(67) | |||||
| (64)LLYYTE(69) | |||||
| (83)NHVTLS(88) | 83–89 | ||||
| (83)NHVTLSQ(89) | |||||
| (91)KIVKWD(96) | 91–96 | ||||
| Acylphosphatase, human muscle | P14621 | 1APSa,b | (16)RVQGVCFRMYTEDEAR(31)b | 16–31 | 28,46,76 |
| (87)SKLEYSNFSIRY(98)b | 87–98 | ||||
| Amphoterin, rat | P63159 | 1CKT | (12)MSSYAFFVQTCREEHK(27) | 12–27 | 77 |
| Apolipoprotein C-II | P02655 | 1SOH | (60)MSTYTGIFTDQ(70) | 60–70 | 22 |
| Cold shock protein, cspB, Bacillus subtilis | P32081 | 2ES2 | (1)MLEGKVKWFNSEKGFGFIEVEG(22) | 1–22 | 78,79 |
| (1)MLEGKVKWFNSEKGFGFIEVEGQDDVFVHFSAIQG(35) | 1–35 | ||||
| (36)EGFKTLEEGQAVSFEIVEGNRGPQAANVTKEA(67) | 36–67 | ||||
| Gelsolin | P06396 | 1KCQ | (182)SFNNGDCFILD(192)c | 182–192 | 80,81 |
| Human complement receptor type 1 | P17927 | 1GKG | (1038)STNRENFHYGSVVTYRS(1054)d | 1038–1054 | 82 |
| Insulin | P01308 | 1XDA | A chain: (13)LYQLEN(18)e | A:13–18 | 75,57 |
| B chain: (11)LVEALY(16)e | B:11–17 | ||||
| B chain: (12)VEALYL(17)e | |||||
| Kerato-epithelin | Q15582 | 1X3Ba | (515)FSMLVAAIQSA(525)f | 515–532f | 83 |
| (515)FSMLVAAIQSAGLTETLN(532)f | |||||
| Lactoferrin | P02788 | 1LFH | (538)NAGDVAFV(545) | 538–545 | 84 |
| Laminin alpha-1 chain, G-like domain, mouse | P19137 | 2JD4 | (2919)SAKVDAIGLEIV(2930) | 2919–2930 | 85 |
| Lysozyme, human | P61626 | 1REX | (56)IFQINS(61) | 56–61 | 86,57 |
| 26–123 | |||||
| 32–108 | |||||
| Medin (a proteolytic fragment of human lactadherin)g | Q08431 | 3BN6g | (299)VTGIITQGAR(308)g | 299–308g | 87 |
| (309)NFGSVQ(314)g | 309–316g | 60,88 | |||
| (309)NFGSVQFV(316)g | |||||
| Myoglobin, horse heart | P68082 | 1WLA | (1)GLSDGEWQQVLNVWGKVEADIAGHGQEVL(29) | 1–29 | 89 |
| (101)IKYLEFISDAIIHVLHSK(118) | 101–118 | 3 | |||
| Prion protein, human, hPrP | P04156 | 1QLX | (113)AGAAAAGAVVGGLGG(127)h,i | 113–127h,i | 90 |
| (132)SAMSRPIIHFGSDYEDRYYRENMHRYPNQ(160)i | 132–160i | 91 | |||
| (138)IIHFGSD(144)i | 138–144i | 57,92 | |||
| (170)SNQNNF(175)i | 170–175i | 57 | |||
| (178)DCVNITIKQHTVTTTT(193)i | 178–193i | 93 | |||
| Prolactin | P01236 | 1RW5 | (7)GAARCQVTLRDLFDR(21) | 7–21 | 94 |
| (20)DRAVVLSHYIHNLSS(34) | 20–34 | ||||
| (43)RYTHGRGFITKAINS(57) | 43–57 | ||||
| RepA of Pseudomonas pPS10 plasmid | Q52546 | 1HKQ | (26)LVLCAASLI(34)j | 26–34 | 95 |
| Transthyretin | P02766 | 1TTA | (105)YTIAALLSPYS(115) | 105–115 | 96,97 |
| The following proteins were found to contain fibril-forming peptides present in previously-characterised amyloidogenic proteinsk: | |||||
| “YjcG” protein, B. subtilis | O31629 | 2D4G | (151)LYQLEN(156) | 151–156 | 57,75 |
| tRNA splicing endonuclease, Methanococcus jannaschii | Q58819 | 1A79 | (47)LVEALYL(53) | 47–53 | |
| DNA polymerase III subunit alpha, Escherichia coli | P10443 | 2HNH | (513)GGVVIA(518) | 513–518 | 57 |
| 20S proteasome Bos taurus (Chains N and 2) | P33672 | 1IRU | (18)GGVVIA(23) | 18–23 | |
| Enterotoxin, Staphylococcus aureus | Q5HHK0 | 2NTT | (50)DFNKF(54) | 50–54 | 61,62 |
| Na+/Ca2+-exchange protein 1, Canis familiaris | P23685 | 2DPK | (455)NFLVH(459) | 455–459 | 98 |
| Cytochrome b Rhodobacter sphaeroides | Q02761 | 2QJP | (337)FGAIL(341) | 337–341 | 63,99 |
| Thymidine kinase, cystolic, human | P04183 | 1W4R | (133)FGAIL(137) | 133–137 | |
| Glycyl-tRNA synthetase, Thermus thermophilus | P56206 | 1ATI | (399)IKVAV(403) | 399–403 | 100,101 |
| Leucine-binding protein, E. coli | P04816 | 1USG | (3)IKVAV(7) | 3–7 | |
Indicates that this is the only suitable model available for the amyloidogenic protein.
1APS is a structural model for equine muscle acylphosphatase, which shares 94% sequence identity with human muscle acylphosphatase. The human sequence, (16)RVQGVCFRMYTEDEAR(31), is (16)RVQGVCFRMYAEDEAR(31) in 1APS; the human sequence (87)SKLEYSNFSIRY(98) is (87)SKLEYSNFSVRY(98) in 1APS.
The 11-peptide containing the mutation D187N has a greatly increased tendency to form amyloid fibrils compared to the peptide with the wild-type sequence with Asp187.80
The native sequence in 1GKG has Cys1054; Ser1054 is reported for the synthetic, fibril-forming peptide.82
The amyloidogenic sequence LVEALYL also occurs the tRNA splicing endonuclease from Methanococcus jannaschii (47)LVEALYL(53), structural model PDB ID:1A79; the amyloidogenic sequence LYQLEN also occurs in the B. subtilis ‘yjcG’ protein (151)LYQLEN(156), structural model PDB ID:2D4G.
Numbering includes 23-residue signal sequence. Amyloidogenic sequence spans Phe21-Asn38 in 1x3B.
The model 3BN6 is bovine lactadherin C2 domain, which shares 70% SID with human lactadherin of which residues 268–317 are medin. Residues Val70-Val87 in 3BN6 are equivalent to the amyloidogenic sequence in human medin between residues 299–316. The human sequence (299)VTGIITQGAR(308) is identical in 3BN6; the human sequence, (309)NFGSVQFV(316), is (80)DFGHIQYV(87) in 3BN6.
Only (125)LGG(127) of this amyloidogenic peptide are represented in structural model 1QLX, the first residue of which is Leu125.
Numbering includes 22-residue signal sequence.
The peptide containing the mutated residue, Val31 is highly amyloidogenic, the wild-type sequence containing Ala31 is amyloidogenic but to a lesser degree.95
Structural models were found by using a Perl program to search the Protein Data Bank for sequences identical to known amyloidogenic peptides (Methods).