Спиральные параметры регулярных-спиралей в белках (часть 2)

Автор: Батхишиг Д., Муиддорж Б., Энхбаяр П.

Журнал: Вестник Бурятского государственного университета. Химия. Физика @vestnik-bsu-chemistry-physics

Рубрика: Химия

Статья в выпуске: 4, 2016 года.

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Α-Cпираль, 310-спираль, π-спираль и -спираль наблюдались в белковых структурах. Они составляют 32% от остатков, 4%, 0,3% и 0,2%, соответственно. Однако эти проценты зависят от разрешения решаемых структур и способу присвоения вторичных структур. Возможно 2016, из отобранного набора в данных банк белков (PDB), содержащих 2901 белковые цепи с менее чем 25% идентичности последовательности и  1.6Å разрешающей способности (R-значения  0.25), использовать в этом анализе. Вторичные задания структуры выполняются DSSP, STRIDE и SECSTR для π-спиралей. Спиральные параметры шага, остатки на оборот, радиусы, хиральности и р = RMSD/(N-1)1/2 для p-спиралей определяются программой HELFIT. р-Значения, оценивающие спиральную регулярность и все π -спиралей с р  0.10Å, были идентифицированы как регулярные. Спиральные параметры белка p-спиралей сравнивались с данными канонических p-спиралей и других типов белковых спиралей.

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Α-спиралей, π-спираль, спиральные параметры, регулярные спирали, белковые структуры

Короткий адрес: https://sciup.org/148317763

IDR: 148317763 | DOI: 10.18101/2306-2363-2016-4-17-25

Текст научной статьи Спиральные параметры регулярных-спиралей в белках (часть 2)

Helix is one of two main types of secondary structures in proteins. Helices are usually designated as in based on the number of residues per turn (i) and the number of atoms in the ring joined by the backbone hydrogen bond (n) [1]. Pauling and Corey first hypothesized the α-helix (3.613) and the γ-helix (5.l17) structures [2]. Donohue later considered the possibility of other types of helices (2.2, 310, 4.314 and 4.416) [3]. Low and Baybutt also suggested the possibility of the 4.416-helix or π-helix [3]. The main stabilizing factor for helical structures in polypeptides is re- peated hydrogen bonds between main chain carbonyl oxygen (C=O) and amide hydrogen (NH) groups with the α-helix characterized by an (i ← i+4) pattern, the 310 and the π-helix by repealing (i ← i+3) and (i ← i+5) hydrogen bonds, respectively [4].

There are several programs perform assignments of secondary structures based on three-dimensional (3D) atomic coordinates of proteins [4-6]. Among these, DSSP [4] and STRIDE [5] are the most widely used [7]. DSSP identifies helices based on the repeating ( i←i+n ) hydrogen bonds with corresponding to n of 3, 4 and 5 for 3 10 , α- and π-helices, respectively [4, 8]. STRIDE uses both hydrogen bonds and main chain dihedral angles to define secondary structures [5]. DSSP program identified only 9 unique π-helices from the database of more than 6000 of proteins [9]. Fodje and Karadaghi defined 116 π-helices using their home made program, SECSTR, from the database of 932 high resolution 3D structures of proteins [7].

These different results can be explained by the following two reasons: 1) Number of solved 3D structures was insufficient by this time 2) Programs to assign of secondary structures use different methods.

We studied helical parameters of protein helices with HELFIT program and compared with the parameters of canonical π -helices.

Materials and Methods

Composition of database

The 16 May 2016 culled PDB data set, containing 2969 protein chains with less than 20% sequence identity and resolution ≤ 1.6 Å ( R -value ≤ 0.25), was used in this analysis.

DSSP program

DSSP performs secondary structure assignments by the bonding energy Е ≤-0.5 kcal/mоl between C=O of residue i and N–H residue n ( i ← i+n ). The optimal hydrogen bonding energy for mainchain-mainchain N—H···O hydrogen bonds Е m < -3 kcal/mol. Hydrogen bond energy depends on both electrostatic interaction N—H···O of atoms and of hydrogen bonds angle θ [4].

STRIDE program

STRIDE program is designed for protein secondary structure assignment from 3D atomic coordinates based on the combined use of hydrogen bond energy and statistically derived backbone torsional angle information [7]. The hydrogen bond energy E hb is calculated using the empirical energy function derived from the analysis of experimental data on hydrogen bond geometries in crystal structures of amino acids in polypeptide chains [10].

SECSTR program

SECSTR is a new addition to the DSSP program that is dedicated to identifying π-helices, which were seldom assigned by older versions of DSSP and STRIDE [7]. The secondary structure assignment methods based on hydrogen bond assignments (DSSP, STRIDE, and SECSTR) produced nearly identical assignments, with more than to 90% [6].

HELFIT program

HELFIT enables to calculate simultaneously all five of the helix parameters with high accuracy. The minimum number of data points required for the analysis is only four. HELFIT also calculates a parameter, p = RMSD / ( N -1)^1/2, which estimates the regularity of helical structures independent of the number of data points, where RMSD is the root mean square distance from the best-fit helix to data points and N is the number of data points [11].

Results and Discussion

We identified 27, 22 and 340 π-helices from 2901 high resolution protein structures by DSSP, STRIDE and SECSTR programs, respectively. All π-helices are divided into two groups, regular and irregular, with p -value: p ≤ 0.10 Å regular and p > 0.10 Å irregular. 7 of 27, 5 of 22, and 76 of 340 helices are grouped as regular by the HELFIT program. In order to compare protein π-helices with the canonical π-helices the only parameters of regular π-helices are used for the further analysis (Table 1).

Table 1

Helical parameters of 86 regular π-helices in proteins identified by DSSP, STRIDE and SECSTR program

PDB _ID	Chain_Po sition	P (Å)	n	Δ z (Å) ^b	r (Å)	V c (Å³) ^a	p (Å)	Identified Program
1DJ0	A_81-87	5.01	4.18	1.20	2.58	25.06	0.10	SECSTR
1DK8	A_242-249	5.12	4.36	1.17	2.69	26.70	0.10	SECSTR
1ELK	A_95-101	5.24	4.42	1.19	2.70	27.15	0.10	SECSTR
1JET	A_301-308	4.82	4.44	1.09	2.80	26.74	0.09	SECSTR
1KJQ	A_119-125	5.10	4.30	1.19	2.67	26.56	0.09	SECSTR
1KK O	A_199-205	4.99	4.53	1.10	2.81	27.33	0.09	DSSP, STRIDE, SECSTR
1NU Y	A_1276-1282	5.30	4.64	1.14	2.87	29.56	0.10	SECSTR
1RK6	A_386-393	5.30	4.47	1.19	2.80	29.20	0.06	DSSP
1RK6	A_387-393	5.14	4.41	1.17	2.74	27.49	0.04	STRIDE
1RK6	A_384-393	5.22	4.37	1.19	2.71	27.56	0.06	SECSTR
1W5 R	A_58-64	5.17	4.37	1.18	2.73	27.70	0.08	SECSTR
1XG0	A_105-111	5.32	4.55	1.17	2.84	29.63	0.10	SECSTR
1XG K	A_266-272	5.02	4.31	1.16	2.70	26.67	0.07	SECSTR
2BF D	A_109-115±	5.20	4.50	1.16	2.80	28.46	0.10	SECSTR
2CI1	A_51-57	5.12	4.33	1.18	2.68	26.68	0.09	SECSTR
2DPL	A_68-74	5.17	4.42	1.17	2.77	28.20	0.03	SECSTR
2GZS	A_163-169	5.31	4.53	1.17	2.83	29.49	0.09	SECSTR

PDB _ID	Chain Po Δ z V Identified Pro P (Å) n r (Å) ^c p (Å) sition (Å) ^b (Å³) ^a gram
2H1V	₂^A₇^_₄^264- 5.15 4.21 1.22 2.62 26.38 0.09 ^SECSTR
2JIS 2O0A	A_28-35 5.15 4.42 1.17 2.75 27.68 0.07 SECSTR A 474- _ SFCSTR ₄^A₃^_₀^424- 5.13 4.48 1.15 2.79 28.00 0.08 ^SECSTR
2P51	₂^A₁^_₃^207- 5.15 4.32 1.19 2.71 27.51 0.08 ^SECSTR
2P6 W 2PB D 2POF 2PY Q 2PY X 2PY X 2PY X 2RB K 2VL A 2WQ F 2XR Y 2Y53 3A0Y	₁^A₆^_₀^154- 5.18 4.38 1.18 2.73 27.69 0.08 ^SECSTR ^A_88-94 5.24 4.42 1.19 2.77 28.58 0.09 ^SECSTR A_37-43 5.29 4.52 1.17 2.81 29.03 0.10 SECSTR ^B_61-67 5.17 4.39 1.18 2.76 28.18 0.02 ^DSSP A 737- DSSP ₂^A₃^_₉^232- 5.09 4.42 1.15 2.75 27.36 0.06 ^DSSP ₂^A₃^_₈^232- 5.06 4.42 1.14 2.78 27.80 0.05 ^STRIDE ₂^A₃^_₉^232- 5.08 4.42 1.15 2.75 27.31 0.06 ^SECSTR ₁^A₂^_₉^122- 5.25 4.49 1.17 2.77 28.19 0.09 ^SECSTR ^A_68-77 5.27 4.00 1.32 2.79 32.22 0.09 ^SECSTR ^A_59-65 5.36 4.55 1.18 2.81 29.22 0.10 ^SECSTR ₃^A₀^_₆^300- 5.20 4.34 1.20 2.70 27.44 0.08 ^SECSTR A_48-54 5.11 4.23 1.21 2.62 26.05 0.10 SECSTR ₇^A₂^_₉^723- 5.11 4.32 1.18 2.70 27.09 0.06 ^SECSTR
3BH Q 3H9C	₁^A₃^_₄^128- 5.07 4.40 1.15 2.77 27.78 0.08 ^SECSTR ₃^A₉^_₁^382- 5.28 4.44 1.19 2.75 28.25 0.09 ^SECSTR
3IT3 3OAJ 3OCJ	A_56-63 5.16 4.45 1.16 2.80 28.56 0.04 SECSTR A_24-30 4.97 4.29 1.16 2.72 26.93 0.07 SECSTR ₂^A₅^_₉^253- 5.13 4.62 1.11 2.88 28.93 0.10 ^SECSTR
3OY V 3PB6 3PJP	₂^A₃^_₃^227- 5.49 4.41 1.24 2.74 29.36 0.08 ^SECSTR X_93-99 5.25 4.54 1.16 2.83 29.10 0.06 SECSTR А 1334- _ SFCSTR ₁^A₃^_₄¹₀^334- 5.18 4.44 1.17 2.77 28.12 0.10 ^SECSTR
3Q28	₂^A₈^_₆^280- 5.30 4.50 1.18 2.81 29.22 0.08 ^SECSTR
3RRI 3S5 M 3T4L	A_22-28 5.17 4.43 1.17 2.77 28.13 0.06 SECSTR ₆^A₉^_₈^692- 5.24 4.45 1.18 2.76 28.18 0.09 ^SECSTR ₁^A₇^_₄^168- 5.29 4.45 1.19 2.77 28.66 0.05 ^SECSTR
3VE N 3WA 2	A 437- _ SFCSTR ₄^A₄^_₃^437- 5.14 4.41 1.17 2.75 27.69 0.10 ^SECSTR X 797- _ DSSP ₃^X₀^_₃^297- 5.04 4.25 1.19 2.68 26.76 0.10 ^DSSP

PDB _ID	Chain_Po sition	P (Å)	n	Δ z (Å) ^b	r (Å)	V c (Å³) ^a	p (Å)	Identified Program
3ZB O	A_94-100	5.22	4.50	1.16	2.82	28.98	0.08	SECSTR
4AY O	A_122-128	5.18	4.28	1.21	2.65	26.70	0.10	SECSTR
4B1Y	B_88-94	5.22	4.42	1.18	2.76	28.26	0.09	SECSTR
4BR C	A_359-365	5.06	4.35	1.16	2.76	27.84	0.05	SECSTR
4CB U	A_89-95	5.22	5.07	1.03	2.72	23.93	0.06	SECSTR
4CD5	A_248-254	5.11	4.38	1.17	2.75	27.72	0.07	SECSTR
4CD5	A_350-356	5.25	4.55	1.15	2.81	28.62	0.09	SECSTR
4DJA	A_305-311	4.99	4.32	1.16	2.73	27.05	0.09	SECSTR
4DJA	A_405-412	5.10	4.39	1.16	2.75	27.60	0.10	SECSTR
4ES M	A_137-143	5.36	4.14	1.29	2.59	27.28	0.07	SECSTR
4EZI	A_128-135	5.02	4.35	1.15	2.72	26.82	0.09	SECSTR
4GV F	A_231-239	5.19	4.46	1.16	2.76	27.85	0.06	DSSP
4GV F	A_232-238	5.14	4.46	1.15	2.80	28.39	0.07	STRIDE
4GV F	A_229-239	5.16	4.44	1.16	2.77	28.01	0.05	SECSTR
4I3G	A_257-264	5.13	4.36	1.18	2.73	27.55	0.08	DSSP
4I3G	A_257-263	5.12	4.40	1.16	2.74	27.45	0.09	STRIDE
4I3G	A_253-264	5.21	4.38	1.19	2.71	27.44	0.09	SECSTR
4JA8	A_66-72	5.29	4.53	1.17	2.85	29.80	0.10	SECSTR
4LRT	A_267-273	5.28	4.46	1.18	2.78	28.74	0.09	SECSTR
4ME 2	A_192-198	4.86	4.47	1.09	2.81	26.97	0.09	SECSTR
4QB3	A_66-72	5.08	4.53	1.12	2.84	28.42	0.09	SECSTR
4R75	A_311-318	5.11	4.38	1.17	2.74	27.52	0.09	SECSTR
4U9H	L_127-133	5.07	4.54	1.12	2.85	28.50	0.07	SECSTR
4W7 L	A_373-379	5.23	4.53	1.15	2.81	28.64	0.08	SECSTR
4WRI	A_65-71	5.18	4.38	1.18	2.73	27.69	0.06	SECSTR
4XE M	A_120-126	5.15	4.33	1.19	2.69	27.04	0.08	SECSTR
4XFJ	A_68-74	5.30	4.45	1.19	2.74	28.09	0.10	SECSTR
4XQ7	A_217-223	5.17	4.49	1.15	2.79	28.16	0.09	SECSTR
4Z5S	A_108-115	5.22	4.40	1.19	2.73	27.78	0.09	SECSTR
4ZG W	A_115-121	5.29	4.53	1.17	2.80	28.76	0.10	SECSTR


PDB _ID	Chain_Po sition	P (Å)	n	Δ z (Å) ^b	r (Å)	V c (Å³) ^a	p (Å)	Identified Program
5A0Y	A_314-324	5.09	4.46	1.14	2.77	27.51	0.10	SECSTR
5AZ B	A_203-210	5.15	4.41	1.17	2.74	27.54	0.09	SECSTR
5BSR	A_240-247	5.12	4.33	1.18	2.68	26.68	0.10	SECSTR
5DA W	A_89-95	5.32	4.37	1.22	2.72	28.30	0.09	SECSTR
5DP2	A_143-149	5.18	4.44	1.17	2.78	28.33	0.06	SECSTR
5E8X	A_442-448	5.09	4.35	1.17	2.74	27.60	0.08	SECSTR
5EJ8	A_485-491	5.22	4.55	1.15	2.81	28.46	0.10	SECSTR
5HZ7	A_280-286	5.25	4.49	1.17	2.80	28.80	0.08	SECSTR
	Average	5.17±0	4.42±0	1.17±0	2.75±0	27.89±	0.08±0
	Average	.11	.13	.04	.06	1.09	.02
Canonical π-helix		5.16	4.40	1.15	2.68	25.9
^a Voronoi volume ( V c = π·			r ²·Δz);	^b Helix rise per residue Δ z			=P / n ;

Total of 88 regular π-helices are 7, 5 and 76 identified by DSSP, STRIDE and SECSTR program respectively. The π-helix is identified at position 199-205 of A chain in 1KKO protein by the three programs [12-18].

Helix radius and Voronoi volume of real π-helices are larger than that of canonical π-helix. The other helix parameters are close to the parameters of canonical π-helix. Average length is 7.47 residues and length is in range of 7-12 residues (Table 2).

Table 2

Average of helical parameters for regular π-helices in proteins and standard deviations

Average	‹ P › (Å)	‹ n ›	‹Δ z ›(Å)	‹ r › (Å)	‹ V c ›(Å³)	‹ p › (Å)
π-helices	5.13±0.	4.41±0.	1.16±0.	2.76±0.	27.75±0.	0.07±0.
(DSSP)	10	09	03	04	78	03
π-helices	5.09±0.	4.44±0.	1.15±0.	2.77±0.	27.69±0.	0.07±0.
(STRIDE)	06	05	02	03	38	02
π-helices	5.17±0.	4.42±0.	1.17±0.	2.75±0.	27.90±1.	0.08±0.
(SECSTR)	11	13	04	06	13	02

Standard deviations of helical parameters for π-helices identified by SECSTR program are larger than DSSP and STRIDE programs. Also, average values of the helix radius r and number of residue per turn n are approximate to each for the three programs.

Fig. The Ramachandran-map of regular π-helices in proteins. The φ, ψ angles are indicated in panels which regular π-helices identified by A) DSSP, B) STRIDE and C) SECSTR, respectively. The abscissa is φ; the ordinate axis is ψ. The φ, ψ of residues at N c and C c are not shown.

Average dihedral angles of regular π-helices were determined at each for DSSP (-77°±14°, -50°±11°), STRIDE (-77°±15°, -51°±12°) and SECSTR (-81°±18°, -44°±21°) programs. The average values of backbone dihedral angles (φ, ψ) of all regular π-helices observed were found to be (φ, ψ) = (-81°, -45°) with standard deviations (σ φ , σ ψ ) = (17°, 20°). The average of dihedral angle is larger than canonical π-helix (-57°, -70°). The φ, ψ angles of regular π-helices are located on an allowed regions for other residues except for glycine, were removed from the calculation (Fig.).

Conclusion

• 2901 3D structures of high resolution protein structures were downloaded

from Protein Data Bank (PDB) and there are 389 π-helices. In average, every protein contains 0.13 π-helices.

• All π-helices are divided into two groups, regular and irregular. 89 π-helices are regular among the total of 389 π-helices, 4.37%. Helix parameters of all regular π-helices are used for further analysis.
• Radii of all π-helices and Voronoi volume are larger than that of canonical π-helices and all the helical parameters are comparable with those of canonical helices.

Список литературы Спиральные параметры регулярных-спиралей в белках (часть 2)

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Pauling L., Corey R. B., Branson H. R. The structure of proteins; two hydrogen- bonded helical configurations of the polypeptide chain // Proc. Natl. Acad. Sci. USA. - 1951. - V. 37, № 4. - P. 205-211.
Low B. W., Baybutt R. B. The π-helix a hydrogen bonded configuration of the polypeptide chain // J. of the American Chemical Society. - 1952. - V. 74(22). - P. 5806-5807.
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