Participation of protein sequence termini in crystal contacts

Abstract

The analysis of the crystal packing interactions, in a nonredundant set of high resolution and monomeric globular protein crystal structures, shows that the residues located at the N-and C-termini of the sequence tend to participate in packing interaction more often than expected and that often they interact with each other. Since the sequence termini are, in general, conformationally very flexible and since they host electrical charges of opposite sign, it can be hypothesized that they play a crucial role in the early formation of the nonphysiological contacts that bring to protein crystallization. It is thus not surprising that modest lengthening/shortening of the sequence termini have often a dramatic effect on protein crystallogenesis.

Missing strings of residues in protein crystal structures

“…However, this might reflect their role in crystallogenesis. 15 Surprisingly, we observed an opposite trend in the case of the sequence distance between missing strings and residues of the same polypeptide chains that are involved in crystal packing interactions. These sequence separations tend to be slightly larger in crystal structures at low resolution.…”

Packing bridges in protein crystal structures

“…By considering also that in most of the cases (95%) a packing bridge connects only two protein molecules and not more than two, we presume that random encounters of two protein molecules in solution may be stabilized by an exogenous small molecule that bridges them and behaves as a template for the nucleation of nascent protein crystals. Interestingly, this phenomenon resembles the role of the N-and C-terminal segments in the formation of nascent crystal packing contacts (Carugo, 2011): given their conformational flexibility, these polypeptide segments are prone to make contacts with adjacent molecules in solution and therefore favour the nucleation processes.…”

Frequency of Dipeptides and Antidipeptides

“…These comparison were performed on a non redundant set of 1758 protein crystal structures (maximal pairwise sequence identity = 20%, crystallographic resolution not worse than 1.6 Å and R factor not worse than 0.25) created with the PISCES web server [10] and where structures with missing atoms or residues (a phenomenon much more common that usually thought [15]) were disregarded.…”

“…For this reason, a series of comparison were made between the dipeptides shown in Tables 3 and 6 (EP/PE, PW/WP, MW/WM, GP/PG, AM/MA, IP/PI, CP/PC, EN/NE), which have a different frequency of occurrence, and the results were compared to the molecular dynamics simulations of another set of pairs of dipeptides (AR/RA, CD/DC, DV/VD, EY/YE, FT/TF, HT/TH, PR/RP, ST/TS) that did not show any difference in their C 190 values or in their propensity values. These comparison were performed on a non redundant set of 1758 protein crystal structures (maximal pairwise sequence identity = 20%, crystallographic resolution not worse than 1.6 Å and R factor not worse than 0.25) created with the PISCES web server [ 10 ] and where structures with missing atoms or residues (a phenomenon much more common that usually thought [ 15 ]) were disregarded.…”