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PDBsum entry 2hkd

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De novo protein PDB id
2hkd
Jmol
Contents
Protein chain
315 a.a. *
Ligands
PG4
Waters ×426
* Residue conservation analysis
PDB id:
2hkd
Name: De novo protein
Title: The crystal structure of engineered ospa
Structure: Outer surface protein a. Chain: a. Engineered: yes. Mutation: yes
Source: Borrelia burgdorferi. Lyme disease spirochete. Organism_taxid: 139. Gene: ospa. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
1.60Å     R-factor:   0.198     R-free:   0.237
Authors: K.Makabe,V.Terechko,S.Koide
Key ref:
K.Makabe et al. (2006). Atomic structures of peptide self-assembly mimics. Proc Natl Acad Sci U S A, 103, 17753-17758. PubMed id: 17093048 DOI: 10.1073/pnas.0606690103
Date:
03-Jul-06     Release date:   21-Nov-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q45040  (Q45040_BORBG) -  Outer surface protein A
Seq:
Struc:
273 a.a.
315 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 81 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cell outer membrane   1 term 

 

 
DOI no: 10.1073/pnas.0606690103 Proc Natl Acad Sci U S A 103:17753-17758 (2006)
PubMed id: 17093048  
 
 
Atomic structures of peptide self-assembly mimics.
K.Makabe, D.McElheny, V.Tereshko, A.Hilyard, G.Gawlak, S.Yan, A.Koide, S.Koide.
 
  ABSTRACT  
 
Although the beta-rich self-assemblies are a major structural class for polypeptides and the focus of intense research, little is known about their atomic structures and dynamics due to their insoluble and noncrystalline nature. We developed a protein engineering strategy that captures a self-assembly segment in a water-soluble molecule. A predefined number of self-assembling peptide units are linked, and the beta-sheet ends are capped to prevent aggregation, which yields a mono-dispersed soluble protein. We tested this strategy by using Borrelia outer surface protein (OspA) whose single-layer beta-sheet located between two globular domains consists of two beta-hairpin units and thus can be considered as a prototype of self-assembly. We constructed self-assembly mimics of different sizes and determined their atomic structures using x-ray crystallography and NMR spectroscopy. Highly regular beta-sheet geometries were maintained in these structures, and peptide units had a nearly identical conformation, supporting the concept that a peptide in the regular beta-geometry is primed for self-assembly. However, we found small but significant differences in the relative orientation between adjacent peptide units in terms of beta-sheet twist and bend, suggesting their inherent flexibility. Modeling shows how this conformational diversity, when propagated over a large number of peptide units, can lead to a substantial degree of nanoscale polymorphism of self-assemblies.
 
  Selected figure(s)  
 
Figure 2.
Fig. 2. Structures of -repeat segments in PSAMs. (A) The backbone structure of the -repeat segment in the crystal structure of OspA+3bh-sm1. The hydrogen bonds between backbone atoms are shown as dashed lines. (B) Side chain conformations of the -repeat segment of OspA+3bh. Only the residues on the front face of the -sheet are shown. The -sheet backbone is shown as arrows. For clarity, the turn regions are omitted. The three cross-strand amino acid ladders are labeled with their respective amino acid compositions ("F/L," "E/K," and "T/I"). These ladders extend short and/or imperfect ones present in wild-type OspA ("FLFV," "EKEK," and "TVTI," respectively) (14). (C) Superposition of a total of 26 copies of the -hairpin unit from the PSAM crystal structures. The backbone of the original -hairpin unit from wild-type OspA is shown in green. Amino acid resides in the -strand regions are labeled with an uppercase letter and residue number. Strand residues labeled in black have their side chain pointing toward the reader, and those labeled in gray have their side chain pointing away from the reader. Residues in the turn regions are labeled with a lowercase letter.
Figure 4.
Fig. 4. Demonstration of the propagation of small conformational differences of -hairpin pairs (i.e., four-stranded building blocks) leading to substantial -ribbon polymorphism. Larger peptide self-assemblies were modeled using six representative -hairpin pairs. Different building blocks are shown in different colors (cyan, 5bh molecule C, -hairpin units 4 and 3; blue, 5bh molecule A, units 3 and2; yellow, 5bh molecule A, units 5 and 4; green, 5bh molecule C, units 3 and 2; red, 2bh units 2 and 1), and only the backbone traces of the -strand regions are shown for clarity. These -hairpin pairs were superimposed using the first two -strands (labeled with "1" and "2," respectively). Different relative orientations of the third and fourth -strands, with respect to the first and second, are evident. -Ribbon superstructures shown at Right were constructed in a step-wise manner. Starting from a four-stranded building block, a copy of the building block was generated. The third and fourth -strands of the original block and the first and second -strands of the copy (which have the identical sequence and nearly identical conformation; Fig. 2C) were then superimposed. In this way, the third and fourth -strands of the copy are now placed as the fifth and sixth -strands of the original building block, and the relative orientation between adjacent two-stranded units (i.e., -strands 1–2 and 3–4, and -strands 3–4 and -strand 5–6) is kept identical. These steps were iterated until a superstructure of sufficient length was generated.
 
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20091870 J.P.Jung, J.Z.Gasiorowski, and J.H.Collier (2010).
Fibrillar peptide gels in biotechnology and biomedicine.
  Biopolymers, 94, 49-59.  
20133689 M.Biancalana, K.Makabe, and S.Koide (2010).
Minimalist design of water-soluble cross-beta architecture.
  Proc Natl Acad Sci U S A, 107, 3469-3474.
PDB codes: 3cka 3eex
20085717 X.Yu, J.Wang, J.C.Yang, Q.Wang, S.Z.Cheng, R.Nussinov, and J.Zheng (2010).
Atomic-scale simulations confirm that soluble beta-sheet-rich peptide self-assemblies provide amyloid mimics presenting similar conformational properties.
  Biophys J, 98, 27-36.  
21031399 Y.Hu, B.Su, C.S.Kim, M.Hernandez, A.Rostagno, J.Ghiso, and J.R.Kim (2010).
A strategy for designing a peptide probe for detection of β-amyloid oligomers.
  Chembiochem, 11, 2409-2418.  
19580739 J.T.Berryman, S.E.Radford, and S.A.Harris (2009).
Thermodynamic description of polymorphism in Q- and N-rich peptide aggregates revealed by atomistic simulation.
  Biophys J, 97, 1.  
19038267 M.Biancalana, K.Makabe, A.Koide, and S.Koide (2009).
Molecular mechanism of thioflavin-T binding to the surface of beta-rich peptide self-assemblies.
  J Mol Biol, 385, 1052-1063.
PDB code: 3ec5
19686665 Y.Miller, B.Ma, and R.Nussinov (2009).
Polymorphism of Alzheimer's Abeta17-42 (p3) oligomers: the importance of the turn location and its conformation.
  Biophys J, 97, 1168-1177.  
18367205 K.Makabe, M.Biancalana, S.Yan, V.Tereshko, G.Gawlak, H.Miller-Auer, S.C.Meredith, and S.Koide (2008).
High-resolution structure of a self-assembly-competent form of a hydrophobic peptide captured in a soluble beta-sheet scaffold.
  J Mol Biol, 378, 459-467.
PDB code: 2i5v
18762191 M.Biancalana, K.Makabe, A.Koide, and S.Koide (2008).
Aromatic cross-strand ladders control the structure and stability of beta-rich peptide self-assembly mimics.
  J Mol Biol, 383, 205-213.
PDB codes: 2oy7 2oy8 2oyb
17718715 A.A.Reinke, and J.E.Gestwicki (2007).
Structure-activity relationships of amyloid beta-aggregation inhibitors based on curcumin: influence of linker length and flexibility.
  Chem Biol Drug Des, 70, 206-215.  
17675353 J.Zheng, H.Jang, B.Ma, C.J.Tsai, and R.Nussinov (2007).
Modeling the Alzheimer Abeta17-42 fibril architecture: tight intermolecular sheet-sheet association and intramolecular hydrated cavities.
  Biophys J, 93, 3046-3057.  
17985889 K.Makabe, S.Yan, V.Tereshko, G.Gawlak, and S.Koide (2007).
Beta-strand flipping and slipping triggered by turn replacement reveal the opportunistic nature of beta-strand pairing.
  J Am Chem Soc, 129, 14661-14669.
PDB codes: 2ol6 2ol7 2ol8 2oy1
17335845 S.Yan, G.Gawlak, K.Makabe, V.Tereshko, A.Koide, and S.Koide (2007).
Hydrophobic surface burial is the major stability determinant of a flat, single-layer beta-sheet.
  J Mol Biol, 368, 230-243.
PDB code: 2i5z
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.