How reverse turns may mediate the formation of helical segments in proteins: an x-ray model.

Perczel, A; Foxman, Bruce M.; Fasman, G. D.

doi:10.1073/pnas.89.17.8210

Cited by 30 publications

(13 citation statements)

References 30 publications

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“…Once started, this might propagate, zipping up the sequence into a 310 helix that could then rearrange to an a-helix. Such a role for p-turns acting as a conformational template for a-helix formation has recently been supported by studies on the crystal structure of (Boc)-Val-Ser-NHCH3 (30). The precise physical means by which this is effected, once understood, may help to throw more light on the determinism of the folding process and the degree to which such folding motifs may be involved.…”

Section: Discussionmentioning

confidence: 80%

Primary structure elements responsible for the conformational switch in the envelope glycoprotein gp120 from human immunodeficiency virus type 1: LPCR is a motif governing folding.

Reed

Kinzel

1993

Proc. Natl. Acad. Sci. U.S.A.

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The ability to undergo a particular conformational switch on moving from a polar to a less polar environment has been shown to be conserved at the CD4-binding domain of the envelope glycoprotein gpl20 from human immunodeficiency virus type 1 despite considerable variability in primary structure and is essential for the process of binding to the T-ceil receptor CD4. The elements necessary to the expression of this behavior have been examined in synthetic peptides using circular dichroism and have been found to include a tetrad, LPCR, plus a tryptophan at a position 8 residues C-terminal to it. In the absence of the tryptophan the conformational change from (sheet to a-helix as medium polarity decreases does not occur abruptly but, rather, in a linear fashion. In the absence of the LPCR tetrad, no transition to a-helix occurs even at 100% trifluoroethanol.These two domains interact to control not only the (3 --a transition but also both its cooperativity and the critical point on the polar -> apolar gradient at which it occurs. Sequence similarity searches of the protein data banks suggest that an LPCR tetrad, governing the folding behavior of subsequent residues, may occur as a conserved motif in proteins in general.

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Section: Discussionmentioning

confidence: 80%

Primary structure elements responsible for the conformational switch in the envelope glycoprotein gp120 from human immunodeficiency virus type 1: LPCR is a motif governing folding.

Reed

Kinzel

1993

Proc. Natl. Acad. Sci. U.S.A.

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“…helix conformation has been demonstrated to be distinctively accessible to the AIS region (34). This order of events also supports the idea that a -turn-like conformation may serve as a conformational template for the formation of helical structure (51).…”

Section: The Fp-ais Interaction Stabilizes Type I -Turn Structuresmentioning

confidence: 79%

Structural Analysis and Assembly of the HIV-1 Gp41 Amino-Terminal Fusion Peptide and the Pretransmembrane Amphipathic-At-Interface Sequence

et al. 2006

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The amino-terminal region within the HIV-1 gp41 aromatic-rich pretransmembrane domain is an amphipathic-at-interface sequence (AIS). AIS is highly conserved between different viral strains and isolates and recognized by the broadly neutralizing 2F5 antibody. The atomic structure of the native Fab2F5-bound AIS appears to involve a nonhelical extended region and a beta-turn structure. We previously described how an immunogenic complex forms, based on the stereospecific interactions between AIS and the gp41 amino-terminal fusion peptide (FP). Here, we have analyzed the structure generated by these interactions using synthetic hybrids containing AIS and FP sequences connected through flexible tethers. The monoclonal 2F5 antibody recognized FP-AIS hybrid sequences with an apparently higher affinity than the linear AIS. Indeed, these hybrids exhibited a weaker capacity to destabilize membranes than FP alone. A combined structural analysis, including circular dichroism, infrared spectroscopy, and two-dimensional infrared correlation spectroscopy, revealed the existence of specific conformations in FP-AIS hybrids, predominantly involving beta-turns. Thermal denaturation studies indicated that FP stabilizes the nonhelical folded AIS structure. We propose that the assembly of the FP-AIS complex may act as a kinetic trap in halting the capacity of FP to promote fusion.

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“…In our fragments, the carbonyl of the first residue points somewhat out of the plane of the turn, where it is more accessible for the bridging interaction with the water molecule, and is more aligned in the direction of a helical hydrogen bond. Model peptides demonstrating a similar conformation have been used to support the idea of ,3-turns as intermediates in the formation of helical structures (23). The fragments in conformation 4bl are somewhat farther from the helix region than those in conformation 4al.…”

Section: Resultsmentioning

confidence: 99%

Significance of bound water to local chain conformations in protein crystals.

Robert

1995

Proc. Natl. Acad. Sci. U.S.A.

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We examine how the polypeptide chain in protein crystal structures exploits the multivalent hydrogenbonding potential of bound water molecules. This shows that multiple interactions with a single water molecule tend to occur locally along the chain. A distinctive internal-coordinate representation of the local water-binding segments reveals several consensus conformations. The fractional water occupancy of each was found by comparison of the total number of conformations in the database regardless of the presence or absence of bound water. The water molecule appears particularly frequently in type II a-turn geometries and an N-terminal helix feature. This work constitutes a first step into assessing not only the generality but also the significance of specific water binding in globular proteins.Aqueous solvation has repeatedly revealed itself to be a fundamental factor in the stability and dynamics of macromolecules (e.g., refs. 1-4). As we continually improve our ability to observe the solvation of macromolecules (5-7), to describe its thermodynamics (2, 8), and to model solvent in atomic detail (e.g., ref. 9), we can expect to uncover more of water's influence in macromolecular behavior. It is natural to ask how this peculiar solvent interacts with proteins, but in this paper we turn the question on its head and ask how the polypeptide chain interacts with water. This exercise is not as formal as it may sound. Unlike small molecules, flexible polymers can adapt to the multivalent hydrogen-bonding capacity of water molecules by taking on a wide variety of conformations. How proteins optimize these interactions reflects on their native stability and on the folding process itself.Studies of bound water in crystal structures have elucidated several themes. Water molecules tend to complete hydrogenbonding patterns of individual chemical groups and of secondary structures (10,11). In a series of homologous proteases, a conserved water molecule can be seen to replace an internal polar group to satisfy particular hydrogen-bonding requirements (12). Bound water can also be associated with various degrees of distortion of secondary structural elements, perhaps revealing a continuum of folding intermediates (13,14), and combined crystallographic and calorimetric studies suggest that structurally integrated water molecules can stabilize the a-helix (15).To place such observations into context, we have studied more generally how proteins in crystal structures incorporate water molecules into their folded states. We see that water complexation is typically a function of short sequence distances and, further, that the bridged polypeptide backbone tends to take on just a few preferred conformations. By examining how many such "water-competent" conformations are actually associated with water in the database, we discovered that those with the highest water occupancy are an N-terminal helix feature and type II 3-turns. These conformations may exemplify structures whose hydrogen-bonding potentials are more difficult to s...

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How reverse turns may mediate the formation of helical segments in proteins: an x-ray model.

Abstract: The three-dimensional structure of a protein is the assembly of diferent scna strutural elements, such as a-helices, 3-pleated sheets, and -turns.

Cited by 30 publications

References 30 publications

Primary structure elements responsible for the conformational switch in the envelope glycoprotein gp120 from human immunodeficiency virus type 1: LPCR is a motif governing folding.

Primary structure elements responsible for the conformational switch in the envelope glycoprotein gp120 from human immunodeficiency virus type 1: LPCR is a motif governing folding.

Structural Analysis and Assembly of the HIV-1 Gp41 Amino-Terminal Fusion Peptide and the Pretransmembrane Amphipathic-At-Interface Sequence

Significance of bound water to local chain conformations in protein crystals.

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